BENZYL N-(2-HYDROXYETHYL)CARBAMATE

White powder

(1) [2-(t-Butyldiphenylsilyloxy)ethyl]carbamic acid benzyl ester [1515] To a solution of aminoethanol (2.0 g, 32.7 mmol) in methylene chloride (60 ml) were added chloroformic acid benzyl ester (5.6 ml, 41.3 mmol) and triethylamine (5.5 ml, 39.5 mmol) in an ice bath. The mixture was stirred at room temperature for 1 hour. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using toluene:acetonitrile (3:2) as the eluant to afford (2-hydroxyethyl)carbamic acid benzyl ester (5.37 g, yield 840percent) as a white solid. [1516] Subsequently, to a solution of (2-hydroxyethyl)carbamic acid benzyl ester (5.37 g, 27.5 mmol) in dimethylformamide (160 ml) were added t-butyldiphenylsilyl chloride (8.6 ml, 33.0 mmol) and imidazole (2.3 g, 33.8 mmol) in an ice bath, and the mixture was stirred at room temperature overnight. After checking the completion of the reaction, ethanol was added thereto and the reaction mixture was stirred for 2 hours. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using hexane:ethyl acetate (5:1) as the eluant to afford [2-(t-butyldiphenylsilyloxy)ethyl]carbamic acid benzyl ester (11.93 g, yield 100percent) as a colorless and transparent syrup. [1517] 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.64 (4H, d, J=6.8 Hz), 7.46-7.28 (12H, m), 5.10 (2H, s), 3.73 (2H, t, J=4.9 Hz), 3.35 (2H, q, J=4.9 Hz), 1.05 (9H, s).32 g (527.5 mmol) of 2-aminoethanol was dissolved in 250 mL of dichloromethane, 300 mL of an aqueous 1N NaOH solution was added thereto, and 60 g (351.7 mmol) of Cbz-Cl (benzyl chloroformate) was slowly added dropwise while the resulting solution was stirred. The resultant solution was stirred at room temperature for 2 hours, an organic layer was separated therefrom and washed twice with water, and the washed organic layer was dehydrated using anhydrous sodium sulfate and concentrated under reduced pressure to obtain 62 g (317.6 mmol) of Compound VI as a white solid (yield: 90percent). [0086] Preparation of Compound VI 32 g (527.5 mmol) of 2-aminoethanol was dissolved in 250 mL of dichloromethane, 300 mL of an aqueous 1N NaOH solution was added thereto, and 60 g (351.7 mmol) of Cbz-Cl (benzyl chloroformate) was slowly added dropwise while the resulting solution was stirred. The resultant solution was stirred at room temperature for 2 hours, an organic layer was separated therefrom and washed twice with water, and the washed organic layer was dehydrated using anhydrous sodium sulfate and concentrated under reduced pressure to obtain 62 g (317.6 mmol) of Compound VI as a white solid (yield: 90percent). [0097] A solution of ethanolamine (4 g, 65.48 mmoles, Aldrich) in 10percent Na75-1) 82-1) EXAMPLE 34 Compound 16, benzyl (2-hydroxyethvl)carbamate, was prepared using a previously reported protocoi.(M. Yar, S. P. Fritz, P. 1 Gates. F. M, McGarrigie. V. K. Aggarwal, Fur. J. Org. Chem, 2012, 160—166) Compound 17. benzyi (2- (((benzyloxy)(diisopropyiarnino)phosphanyl)oxv) ethyl)carbaniate, was prepared using previously reported protocol (P. W. Rzepecki, G. D. Prestwich, I Org. Chemn. 2002, 67, 5454-- 5460). Compound (18):To a stirred solution of ethanolamine (4.0 g, 66 mmol) in DCM (4 mL) was added benzyl chloroformate (4.6 mL, 33 mmol) at 0° C. After 1 h, the reaction mixture was warmed to room temperature and washed with 1.0N HCl (40 mL) and water (40 mL). The organics were separated, dried with anhydrous sodium sulfate, filtered, and concentrated. To a solution of the crude product in ethyl acetate (30 mL) was added hexanes (30 mL). The resulting crystals were filtered and dried to give the title intermediate as a white solid (4.5 g, 70percent). 2-aminoethanol (2.0 g, 32.7 mmol) was dissolved in methylene chloride (110 mL) and benzyloxycarbonyl chloride (5.07 g, 29.8 mmol) and triethylamine (4.44 g, 44.6 mmol) were sequentially added. The resulting solution was stirred for 1 hour at room temperature. Water (40 mL) was added to the resulting solution. The resultant was dehydrated with anhydrous sodium sulfate and concentrated under reduced pressure to yield Compound X (4.05 g (70percent)).2-aminoethanol (2.0 g, 32.7 mmol) was dissolved in methylene chloride (110 mL) and benzyloxycarbonyl chloride (5.07 g, 29.8 mmol) and triethylamine (4.44 g, 44.6 mmol) were sequentially added. The resulting solution was stirred for 1 hour at room temperature. Water (40 mL) was added to the resulting solution. The resultant was dehydrated with anhydrous sodium sulfate and concentrated under reduced pressure to yield Compound X (4.05 g (70percent)). To a stirred solution of 2-aminoethanol (5, 4.94 mL, 81.86 mmol) in CHTo a stirred solution of 2-Aminoethanol (6, 4.94 mL, 81.86 mmol) in CH2Cl2 (50 mL) at 0 °C, triethylamine(22.2 mL, 159.6 mmol) was added dropwise. Benzyloxycarbonylchloride (15.2 mL, 106.42 mmol) was addeddropwise over 30 min. After completion of the addition, the mixture was stirred at 0 °C for 1 h. The mixture wasquenched with water (50 mL) and extracted with CH2Cl2(3 9 50 mL). The combined organic layer extracts werewashed with brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue waspurified by flash column chromatography. The desiredproduct was obtained as white solid (9.5 g, 59 percent). Mp73–75 °C; 1H NMR (CDCl3, 300 MHz) δ 7.34 (s, 5H), 5.73(bs, 1H), 5.10 (s, 2H), 3.74 (s, 2H), 3.29 (bs, 2H); 13C NMR(CDCl3, 75MHz) d 157.2, 136.4, 128.5, 128.1, 128.1, 66.8, 61.7, 43.4; LC-MS: m/z calculated for C10H13NO3:195, Found: 196 (M+1) +.Preparation of Compound 5a To a solution of 2-aminoethanol (10 g, 164 mmol) in DCM (70 mL) were added triethylamine (3.9 mL, 28.1 mmol) and benzyl chloroformate (30 mL, 213 mmol) in DCM (30 mL) at 0 °C under NTo a solution of 2-aminoethanol (10 g, 164 mmol) in DCM (70 mL) were added triethylamine (3.9 mL, 28.1 mmol) and benzyl chloroformate (30 mL, 213 mmol) in DCM (30 mL) at 0 °C under NBenzylchloroformate (44.95 kg, 263.5 mol, 1.0 eq.) was added over a 2 hour period at room temperature to a solution of ethanolamine (16.1 kg, 263.5 mol, 1.0 eq.) in water (34 gal, 128.7 L).. Preparation Five STR31 N-Benzyloxycarbonyl-2-aminoethanol. Preparation Five Preparation Five N-Benzyloxycarbonyl-2-aminoethanol

Molecular Weight:195.21
XLogP3:1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:5
Exact Mass:195.08954328
Monoisotopic Mass:195.08954328
Topological Polar Surface Area:58.6
Heavy Atom Count:14
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes