Heptanoic acid, 6-oxo-, methyl ester

Dissolve 10 g 6-oxoheptanoic acid (69.4 mmol) in 100 ml methanol. A solution of 6-oxoheptanoic acid (4.0 g, 30 mmol) and concentrated HConcentrated HConcentrated H2SO4 (0.2 mL) was added to a stirred solution of 6-oxoheptanoic acid (10 g, 69 mmol) in DCE/MeOH (50 mL/ 20 mL). The mixture was stirred at 90 °C overnight. The solution was cooled to room temperature and concentrated. The residue was diluted with DCM (200 mL), washed with saturated NaHCCb solution, water, brine, dried and concentrated to give methyl 6-oxoheptanoate as light yellow liquid (8.4 g) Yield 76percent (100percent purity, UV = 214 nm, ESI 159 (M+H)+).(1) To a solution of 6-oxoheptanoic acid (99.2 g) in methanol (1 L), concentrated sulfuric acid (20 mL) was added, and the mixture was heated to reflux for 4 hours. The reaction mixture was cooled to room temperature, and then, the solvent was distilled off under reduced pressure. Water (1 L) and ethyl acetate (600 mL) were added to the residue. The organic layer was separated and washed with a 5percent aqueous sodium bicarbonate solution (600 mL) and a saturated aqueous solution of sodium chloride (600 mL), and the solvent was distilled off under reduced pressure to obtain compound (O1) (95.2 g). TLC Rf: 0.45 (hexane/ethyl acetate=2/1)(1)Concentrated sulfuric acid (20 mL)was added to a methanol (1 L)solution of 6-oxopentaonic acid (99.2 g), and the mixture was heated for 4 hours under reflux. After the reaction mixture was cooled to room temperature, the solvent was distilled away under reduced pressure, and water (1 L)and ethyl acetate (600 mL)were added thereto. The organic layer was fractionated and washed with a 5percent aqueous sodium hydrogen carbonate solution (600 mL)and an aqueous saturated sodium chlorides solution (600 mL), and the solvent was distilled away under reduced pressure, thereby obtaining (01)(95.2 g). TLC Rf: 0.45 (hexane/ethyl acetate=2/1)(1)Concentrated sulfuric acid (20 mL) was added to a solution of 6-oxoheptanoic acid (99.2 g) in methanol (1 L)And heated under reflux for 4 hours. After cooling the reaction mixture to room temperature, the solvent was distilled off under reduced pressure, Water (1 L) and ethyl acetate (600 mL) were added.The organic layer was separated, The mixture was washed with a 5percent aqueous sodium hydrogen carbonate solution (600 mL) and a saturated aqueous sodium chloride solution (600 mL), and the solvent was distilled off under reduced pressure to obtain (O1) (95.2 g).Methyl 6-oxoheptanoate (24) A mixture of A mixture of (2) To a mixture of 2-aminonicotinaldehyde (133 g) and methanol (500 mL), compound (O1) (189 g) and methanol (600 mL) were added, then pyrrolidine (100 mL) was added, and the resulting mixture was heated to reflux for 8 hours. The reaction mixture was cooled to room temperature, and the solvent was distilled off under reduced pressure. Then, toluene (100 mL) was added to the residue, and the solvent was distilled off under reduced pressure. To the obtained residue, toluene (150 mL) was added, and the mixture was stirred at 50° C. for 2 hours and then stirred at room temperature for 3 hours. The solid was collected by filtration to obtain compound (O2) (149 g). TLC Rf: 0.56 (ethyl acetate/methanol=5/1) LC/MS (ACQUITY) rt (min): 0.73 MS (ESI, m/z): 245.2 [M+H]+A mixture of 4-2 (1.4 g, 9.04 mmol), 1-3, 2-amino-3-formylpyridine (552 mg, 4.52 mmol) (for preparation, see: J. Org. Chem., 1983, 48, 3401), and proline (260 mg, 2.26mmol) in absolute ethanol (23 mL) was heated at reflux for 18 h. Following evaporative removal of the solvent, the residue was chromatographed (silica gel, 80percent ethyl acetate/hexane, then ethyl acetate) to give ester 4-4 as a white solid.TLC Rf= 0.38 (silica, EtOAc).?HNIVIR (300 IVIHz, CDC13) oe 9.08 (m, 1H), 8.16 (d, J=8.0 Hz, 1H), 8.10 (d, J=8.3 Hz, 1H), 7.45(m, 1H), 7.39 (d, J=8.3 Hz, 1H), 3.66 (s, 3H), 3.08 (t, J=7.6 Hz, 2H), 2.39 (t, J=7.6 Hz, 2H), 1.94(m, 2H), 1.78 (m, 2H).(01)(189 g)and methanol (600 mL)were added to a mixture of 2-aminonicotinaldehyde (133 g)and methanol (500 mL), and then pyrrolidine (100 mL)was added thereto, and the mixture was heated for 8 hours under reflux. The reaction mixture was cooled to room temperature, the solvent was distilled away under reduced pressure, toluene (100 mL)was added thereto, and the solvent was distilled away under reduced pressure. Toluene (150 mL)was added to the obtained residue, followed by stirring for 2 hours at 50° C. and then for 3 hours at room temperature, and the solid was collected by filtration, thereby obtaining (02)(149 g). TLC Rf: 0.56 (hexane/ethyl acetate=5/1)LC/MS rt (min): 0.73 MS (ESI, m/z): 245.2[M+H]+19a-int (21 g, 132.75 mmol), 2-aminopyridine-3-carbaldehyde (17.83 g, 146.03 mmol) and L-proline (7.64 g, 66.38 mmol) in EtOH (200 mL) were stirred at 80 °C for 10 hrs. LCMS showed that the 19b-int was formed. The solvent was removed and the crude product was purified by chromatography on silica gel (PE: EtOAc = 10: 1 to 1:1, Rf= 0.3) to give 19b-int; LCMS (ESI+) : m/z = 245.0 (M+H)+, RT=0.75 min.(2)To a mixture of 2-aminonicotinaldehyde (133 g) and methanol (500 mL)(O1) (189 g) and methanol (600 mL) were added, pyrrolidine (100 mL) was added, And heated under reflux for 8 hours. The reaction mixture was cooled to room temperature, After distilling off the solvent under reduced pressure, toluene (100 mL) was added, and the solvent was distilled off under reduced pressure.Toluene (150 mL) was added to the obtained residue, after stirring at 50 ° C. for 2 hours, The mixture was stirred at room temperature for 3 hours, and the solid was collected by filtration to obtain (O 2) (149 g).

Molecular Weight:158.19
XLogP3:0.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:6
Exact Mass:158.094294304
Monoisotopic Mass:158.094294304
Topological Polar Surface Area:43.4
Heavy Atom Count:11
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes