1,2-Dichloroethane → 3-(4-benzyloxyphenyl)-(S)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)propanoic amide

HRID 432076Notes

Reaction equation

HRID 432076 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([O:20][CH2:21][CH3:22])[C:17]([OH:19])=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1.[CH:46]1[CH:51]=[CH:50][C:49]([CH:52]([NH2:55])[CH2:53][OH:54])=[CH:48][CH:47]=1>ClCCl.CCCCCCC.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C@H:16]([O:20][CH2:21][CH3:22])[C:17]([NH:55][C@H:52]([C:49]2[CH:50]=[CH:51][CH:46]=[CH:47][CH:48]=2)[CH2:53][OH:54])=[O:19])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@@H:16]([O:20][CH2:21][CH3:22])[C:17]([NH:55][C@H:52]([C:49]2[CH:50]=[CH:51][CH:46]=[CH:47][CH:48]=2)[CH2:53][OH:54])=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 924662-Amino-2-phenylethanolHCID 109245703-[4-(Benzyloxy)phenyl]-2-ethoxypropanoic acid

Product 2

HCID 111226333-(4-benzyloxyphenyl)-(R)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)propanoic amideYield 31%HCID 117615803-(4-benzyloxyphenyl)-(S)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)propanoic amideYield 37%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

A solution of 3-(4-benzyloxyphenyl)-2-ethoxypropanoic acid (2.92 g, 9.74 mmole) in dry dichloromethane (30 ml) was cooled on an ice-bath and EDC (2.03 g; 10.61 mmole), diisopropylethylamine (1.84 ml, 10.61 mmole) and HOBt x H2O (1.43 g; 10.61 mmole) were added. After 30 minutes the ice-bath was removed and (R)-phenylglycinol (1.46 g, 10.61 mmole) was added. After stirring at room temperature over night ethyl acetate (100 ml) was added and the mixture was washed with potassium hydrogensulfate (1 M), saturated sodium bicarbonate solution, sodium carbonate solution and brine. The organic phase was dried (sodium sulfate), filtered and the solvent was evaporated in vacuo. The crude product was purified by chromatography on silica gel using ethyl acetate:heptan to give 1.5 g (yield 37%) of 3-(4-benzyloxyphenyl)-(S)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)propanoic amide and 1.25 g (yield 31%) of 3-(4-benzyloxyphenyl)-(R)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)propanoic amide.

Workup

  1. customAfter 30 minutes the ice-bath was removed
  2. additionwas added
  3. washthe mixture was washed with potassium hydrogensulfate (1 M), saturated sodium bicarbonate solution, sodium carbonate solution and brine
  4. dry with materialThe organic phase was dried (sodium sulfate)
  5. filtrationfiltered
  6. customthe solvent was evaporated in vacuo
  7. customThe crude product was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-f9f99cf03405419495913450205c6bd8
Source dataset
uspto-grants-2003_12
Patent number
US06660879B2

Reaction notes

Loading…