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

HRID 279683Notes

Reaction equation

HRID 279683 reaction equation
C(Cl)CCl.C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1.O.[CH2:25]([O:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH:40]([O:44][CH2:45][CH3:46])[C:41]([OH:43])=[O:42])=[CH:35][CH:34]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[CH:47]1[CH:52]=[CH:51][C:50]([CH:53]([NH2:56])[CH2:54][OH:55])=[CH:49][CH:48]=1>ClCCl.CCCCCCC.C(OCC)(=O)C>[CH2:25]([O:32][C:33]1[CH:34]=[CH:35][C:36]([CH2:39][C@H:40]([O:44][CH2:45][CH3:46])[C:41]([NH:56][C@H:53]([C:50]2[CH:51]=[CH:52][CH:47]=[CH:48][CH:49]=2)[CH2:54][OH:55])=[O:43])=[CH:37][CH:38]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1.[CH2:25]([O:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][C@@H:40]([O:44][CH2:45][CH3:46])[C:41]([NH:56][C@H:53]([C:50]2[CH:51]=[CH:52][CH:47]=[CH:48][CH:49]=2)[CH2:54][OH:55])=[O:42])=[CH:35][CH:34]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

11

Reactant 6

HCID 111,2-DichloroethaneHCID 962WaterHCID 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

EDC (2.03 g; 10.61 mmole), diisopropylethylamine (1.84 ml, 10.61 mmole) and HOBt×H2O (1.43 g; 10.61 mmole) were added to a solution of 3-(4-benzyloxyphenyl)-2-ethoxypropanoic acid (2.92 g, 9.74 mmole) in dry dichloromethane (30 ml) on an ice-bath. After 30 minutes the ice-bath was removed and (R)-phenylglycinol (1.46 g, 10.61 mmole) was added. After stirring at room temperature overnight ethyl acetate (100 ml) was added and the solution 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:heptane 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 solution 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-74d42c49009f43ca971d28f2a32b1c50
Source dataset
uspto-grants-2002_03
Patent number
US06362360B1

Reaction notes

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