2-Butenoicacid,3-(acetylamino)-,ethylester,(2E)-

To a 10 mL Pyrex pressure vial for closed vessel formicrowave heating reaction, was added 0.5 mmol of theenaminone 6a and 0.1 mL of acetic anhydride. The mixturewas subjected to heating in a CEM Discover SP reactorat 90 °C and 200 W for 1 minute, with IR temperaturecontrol and medium stirring speed using cylindrical stirbars (10 × 3 mm), default ramp time of 10 min. After thistime, the mixture was cooled to room temperature and then4 mL of distilled water was added. After cooling in therefrigerator the solid product was filtered and washed withcold water, resulting in 56.6 mg of white crystals of 9, 66percentyield; m.p. 61.8-62.2 °C (Lit31 63-65 °C); IR (KBr) n / cm-13224, 3074, 2978, 2929, 1712, 1639, 1500, 1475, 1440, 1385, 1274, 1288, 1176, 1064, 1029, 983, 839, 783, 663, 605; 1H NMR (500 MHz, CDCl3) d 4.87 (d, J 1.0 Hz, NH), 4.14 (q, 2H, J 7.0 Hz, CH2), 2.36 (d, 3H, J 1.0 Hz, CH3), 2.12 (s, 3H, CH3), 1.26 (t, J 7.0 Hz, 3H, CH3); 13C NMR(125 MHz, CDCl3) d 14.2, 21.8, 25.2, 59.8, 96.4, 155.0, 168.9, 169.2.General procedure: A mixture of amides (amines) (0.6 mmol), 1, 3-dicarbonylcompounds (0.5 mmol), and DPAT (0.05 mmol) was stirred in refluxing toluene for 6 h. After completion of the reaction(Reaction progress was monitored by TLC), the mixture was washed with water (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated. Purification by column chromatography on silica gave the product 3, 4, 5.Examples 49 to 62; Preparation of 8-Acetamidoalanine Esters Using Rhodium Metal Complex Catalyst Each substrate for reduction (1.0 mmol) and each metal complex (0.005 mmol) were weighed in a Pyrex (registered trade name) test tube for autoclaving, the tube was set in a 50-mL autoclave together with a stirrer in the tube, and the atmosphere in the autoclave was substituted with nitrogen. The reaction mixture was added with 2 mL of methanol, the atmosphere in the autoclave was sufficiently substituted with hydrogen, and then pressurized with 2 MPa of hydrogen, and the reaction was allowed at 45 C. for 17 hours. After the reaction, the reaction mixture was added with 0.02 g of activated carbon, and stirred for 30 minutes, and after the activated carbon was removed, the reaction mixture was concentrated in an evaporator to quantitatively obtain each beta-acetamidoalanine ester.The resulting 8-acetamidoalanine ester in an amount of 2 mg was dissolved in 1 mL of methanol, and analyzed by GC or HPLC under the following conditions.3-Acetylaminobutanoic acid ethyl ester (R=Me, R'=Et)Analysis conditions: column produced by SPELCO, beta-DEX 325, column temperature: 140 C., injection temperature: 220 C., detector temperature: 300 C., mobile phase:50 kPa of helium, split ratio: 50:1, FID detector, injection: 5 muL, R.T.: S-isomer=25.5 min., R-isomer=26.4 min.1H NMR (300 MHz, CDCl3): delta 6.15 (brs, 1H), 4.39-4.31 (m, 1H), 4.21 (q, 7.2 Hz, 2H), 2.52 (dd, 2.8, 5.3 Hz, 2H), 1.96 (s, 3H), 1.27 (t, J=7.2 Hz, 3H), 1.23 (d, J=6.6 Hz, 3H) 3-Acetylaminopentanoic acid methyl ester (R=Et, R'=Me)Analysis conditions: column produced by SPELCO, beta-DEX 325, column temperature: 120 C., injection temperature: 220 C., detector temperature: 300 C., mobile phase:50 kPa of helium, split ratio: 50:1, FID detector, injection: 5 muL, R.T.: S-isomer=54.4 min., R-isomer=56.0 min.1H NMR (300 MHz, CDCl3): delta 6.09 (brs, 1H), 4.19-4.12 (m, 1H), 3.69 (s, 3H), 2.54 (dd, J=3.8, 5.0 Hz, 2H), 1.99 (s, 3H), 1.62-1.51 (m, 2H), 0.92 (t, J=7.5 Hz, 3H)3-Acetylaminohexanoic acid ethyl ester (R=n-Pr, R'=Et)Analysis conditions: Chiralcel OC produced by Daicel Chemical Industries, Ltd., n-hexane/2-propanol=9/1, 0.5 mL/min., 210 nm, 30 C., R.T.: S-isomer=25.4 min., R-isomer=30.0 min.1H NMR (300 MHz, CDCl3): delta 6.09 (d, J=7.8 Hz, 1H), 4.30-4.19 (m, 1H), 4.15 (q, J=7.2 Hz, 2H), 2.52 (ddd, J=5.1, 15.8, 23.5 Hz, 2H), 1.97 (s, 3H), 1.61-1.29 (m, 4H), 1.25 (t, J=6.8 Hz, 3H), 0.91 (t, J=7.4 Hz, 3H)3-Acetylamino-3-phenylpropanoic acid ethyl ester (R=Ph, R'=Et)Analysis conditions: Chiralcel OD by Daicel Chemical Industries, Ltd., n-hexane/2-propanol=95/5, 1.0 mL/min., 220 nm, 40 C., R.T.: R-isomer=22.5 min., S-isomer=26.0 min.1H NMR (300 MHz, CDCl3): delta 7.36-7.23 (m, 5H), 6.62 (d, J=7.8 Hz, 1H), 5.46-5.40 (m, 1H), 4.06 (q, J=7.8 Hz, 2H), 2.96-2.78 (m, 2H), 2.03 (s, 3H), 1.16 (t, J=7.2 Hz, 3H)Examples 49 to 62; Preparation of 8-Acetamidoalanine Esters Using Rhodium Metal Complex Catalyst Each substrate for reduction (1.0 mmol) and each metal complex (0.005 mmol) were weighed in a Pyrex (registered trade name) test tube for autoclaving, the tube was set in a 50-mL autoclave together with a stirrer in the tube, and the atmosphere in the autoclave was substituted with nitrogen. The reaction mixture was added with 2 mL of methanol, the atmosphere in the autoclave was sufficiently substituted with hydrogen, and then pressurized with 2 MPa of hydrogen, and the reaction was allowed at 45 C. for 17 hours. After the reaction, the reaction mixture was added with 0.02 g of activated carbon, and stirred for 30 minutes, and after the activated carbon was removed, the reaction mixture was concentrated in an evaporator to quantitatively obtain each beta-acetamidoalanine ester.The resulting 8-acetamidoalanine ester in an amount of 2 mg was dissolved in 1 mL of methanol, and analyzed by GC or HPLC under the following conditions.3-Acetylaminobutanoic acid ethyl ester (R=Me, R'=Et)Analysis conditions: column produced by SPELCO, beta-DEX 325, column temperature: 140 C., injection temperature: 220 C., detector temperature: 300 C., mobile phase:50 kPa of helium, split ratio: 50:1, FID detector, injection: 5 muL, R.T.: S-isomer=25.5 min., R-isomer=26.4 min.1H NMR (300 MHz, CDCl3): delta 6.15 (brs, 1H), 4.39-4.31 (m, 1H), 4.21 (q, 7.2 Hz, 2H), 2.52 (dd, 2.8, 5.3 Hz, 2H), 1.96 (s, 3H), 1.27 (t, J=7.2 Hz, 3H), 1.23 (d, J=6.6 Hz, 3H) 3-Acetylaminopentanoic acid methyl ester (R=Et, R'=Me)Analysis conditions: column produced by SPELCO, beta-DEX 325, column temperature: 120 C., injection temperature: 220 C., detector temperature: 300 C., mobile phase:50 kPa of helium, split ratio: 50:1, FID detector, injection: 5 muL, R.T.: S-isomer=54.4 min., R-isomer=56.0 min.1H NMR (300 MHz, CDCl3): delta 6.09 (brs, 1H), 4.19-4.12 (m, 1H), 3.69 (s, 3H), 2.54 (dd, J=3.8, 5.0 Hz, 2H), 1.99 (s, 3H), 1.62-1.51 (m, 2H), 0.92 (t, J=7.5 Hz, 3H)3-Acetylaminohexanoic acid ethyl ester (R=n-Pr, R'=Et)Analysis conditions: Chiralcel OC produced by Daicel Chemical Industries, Ltd., n-hexane/2-propanol=9/1, 0.5 mL/min., 210 nm, 30 C., R.T.: S-isomer=25.4 min., R-isomer=30.0 min.1H NMR (300 MHz, CDCl3): delta 6.09 (d, J=7.8 Hz, 1H), 4.30-4.19 (m, 1H), 4.15 (q, J=7.2 Hz, 2H), 2.52 (ddd, J=5.1, 15.8, 23.5 Hz, 2H), 1.97 (s, 3H), 1.61-1.29 (m, 4H), 1.25 (t, J=6.8 Hz, 3H), 0.91 (t, J=7.4 Hz, 3H)3-Acetylamino-3-phenylpropanoic acid ethyl ester (R=Ph, R'=Et)Analysis conditions: Chiralcel OD by Daicel Chemical Industries, Ltd., n-hexane/2-propanol=95/5, 1.0 mL/min., 220 nm, 40 C., R.T.: R-isomer=22.5 min., S-isomer=26.0 min.1H NMR (300 MHz, CDCl3): delta 7.36-7.23 (m, 5H), 6.62 (d, J=7.8 Hz, 1H), 5.46-5.40 (m, 1H), 4.06 (q, J=7.8 Hz, 2H), 2.96-2.78 (m, 2H), 2.03 (s, 3H), 1.16 (t, J=7.2 Hz, 3H)All operations are performed under argon and with degassed solvents. The hydro- genations are carried out in glass vials (low hydrogen pressure) or in steel autoclaves (high hydrogen pressure). Agitation is effected either by a magnetic stirrer or by All operations are performed under argon and with degassed solvents. The hydro- genations are carried out in glass vials (low hydrogen pressure) or in steel autoclaves (high hydrogen pressure). Agitation is effected either by a magnetic stirrer or by The method of carrying out the hydrogenations and the determination of the optical yields ee is described in general terms by W. Weissensteiner et al in Organometallics 21 (2002), pages 1766-1774. The catalysts are in each case prepared in situ in the solvent by mixing of the ligand and metal complex as catalyst precursor (unless indicated otherwise = [Rh(norbornadiene)2]BF4). Unless indicated otherwise, the substrate concentration is 0.25 mol/l. The determination of conversion and ee of MAA is carried out by means of gas chromatography using a chiral column (Chirasil-L-val).The hydrogenations of EAC are carried out in ethanol in the presence of 5% (v/v) of CF3CH2OH. The determination of the ee is carried out by means of gas chromatography using a chiral column [Lipodex E (30m); 1300C isothermal; 190 KPa H2]. In the hydrogenation of EOV, [Rul2(p-cumene)]2 is used as metal complex and catalyst precursor. The determination of the ee is carried out after reaction with trifluoroacetic anhydride by means of gas chromatography using a chiral column [Lipodex E (30m)].In the hydrogenation of MEA, [Ir(COD)CI]2 is used as metal complex and catalyst precursor. The hydrogenation is carried out in bulk using 105 g of MEA (without solvent) in the presence of 70 mg of tetrabutylammonium iodide and 10 ml of acetic acid.The method of carrying out the hydrogenations and the determination of the optical yields ee is described in general terms by W. Weissensteiner et al in Organometallics 21 (2002), pages 1766-1774. The catalysts are in each case prepared in situ in the solvent by mixing of the ligand and metal complex as catalyst precursor (unless indicated otherwise = [Rh(norbornadiene)2]BF4). Unless indicated otherwise, the substrate concentration is 0.25 mol/l. The determination of conversion and ee of MAA is carried out by means of gas chromatography using a chiral column (Chirasil-L-val).The hydrogenations of EAC are carried out in ethanol in the presence of 5% (v/v) of CF3CH2OH. The determination of the ee is carried out by means of gas chromatography using a chiral column [Lipodex E (30m); 1300C isothermal; 190 KPa H2]. In the hydrogenation of EOV, [Rul2(p-cumene)]2 is used as metal complex and catalyst precursor. The determination of the ee is carried out after reaction with trifluoroacetic anhydride by means of gas chromatography using a chiral column [Lipodex E (30m)].In the hydrogenation of MEA, [Ir(COD)CI]2 is used as metal complex and catalyst precursor. The hydrogenation is carried out in bulk using 105 g of MEA (without solvent) in the presence of 70 mg of tetrabutylammonium iodide and 10 ml of acetic acid.The method of carrying out the hydrogenations and the determination of the optical yields ee is described in general terms by W. Weissensteiner et al in Organometallics 21 (2002), pages 1766-1774. The catalysts are in each case prepared in situ in the solvent by mixing of the ligand and metal complex as catalyst precursor (unless indicated otherwise = [Rh(norbornadiene)2]BF4). Unless indicated otherwise, the substrate concentration is 0.25 mol/l. The determination of conversion and ee of MAA is carried out by means of gas chromatography using a chiral column (Chirasil-L-val).The hydrogenations of EAC are carried out in ethanol in the presence of 5% (v/v) of CF3CH2OH. The determination of the ee is carried out by means of gas chromatography using a chiral column [Lipodex E (30m); 1300C isothermal; 190 KPa H2]. In the hydrogenation of EOV, [Rul2(p-cumene)]2 is used as metal complex and catalyst precursor. The determination of the ee is carried out after reaction with trifluoroacetic anhydride by means of gas chromatography using a chiral column [Lipodex E (30m)].In the hydrogenation of MEA, [Ir(COD)CI]2 is used as metal complex and catalyst precursor. The hydrogenation is carried out in bulk using 105 g of MEA (without solvent) in the presence of 70 mg of tetrabutylammonium iodide and 10 ml of acetic acid.To a 10 mL Pyrex pressure vial for closed vessel formicrowave heating reaction, was added 0.5 mmol of theenaminone 6a and 0.1 mL of acetic anhydride. The mixturewas subjected to heating in a CEM Discover SP reactorat 90 C and 200 W for 1 minute, with IR temperaturecontrol and medium stirring speed using cylindrical stirbars (10 × 3 mm), default ramp time of 10 min. After thistime, the mixture was cooled to room temperature and then4 mL of distilled water was added. After cooling in therefrigerator the solid product was filtered and washed withcold water, resulting in 56.6 mg of white crystals of 9, 66%yield; m.p. 61.8-62.2 C (Lit31 63-65 C); IR (KBr) n / cm-13224, 3074, 2978, 2929, 1712, 1639, 1500, 1475, 1440, 1385, 1274, 1288, 1176, 1064, 1029, 983, 839, 783, 663, 605; 1H NMR (500 MHz, CDCl3) d 4.87 (d, J 1.0 Hz, NH), 4.14 (q, 2H, J 7.0 Hz, CH2), 2.36 (d, 3H, J 1.0 Hz, CH3), 2.12 (s, 3H, CH3), 1.26 (t, J 7.0 Hz, 3H, CH3); 13C NMR(125 MHz, CDCl3) d 14.2, 21.8, 25.2, 59.8, 96.4, 155.0, 168.9, 169.2.

Molecular Weight:171.19
XLogP3:0.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:171.08954328
Monoisotopic Mass:171.08954328
Topological Polar Surface Area:55.4
Heavy Atom Count:12
Complexity:208
Defined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes