Dichloromethane → 5-{[(S)-1-(4-Chloro-phenyl)-ethyl]-methoxycarbonyl-amino}-3-hydroxy-3-phenyl-pentanoic acid methyl ester

HRID 473929Notes

Reaction equation

HRID 473929 reaction equation
[Zn](CC)CC.[CH3:6][O:7][C:8](=[O:29])[N:9]([C@H:20]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)[CH3:21])[CH2:10][CH2:11][C:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Br[CH2:31][C:32]([O:34][CH3:35])=[O:33].ClCCl>ClCCCl>[CH3:35][O:34][C:32](=[O:33])[CH2:31][C:12]([OH:19])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:11][CH2:10][N:9]([C@H:20]([C:22]1[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=1)[CH3:21])[C:8]([O:7][CH3:6])=[O:29]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 60984Methyl bromoacetateHCID 58109487[(S)-1-(4-Chloro-phenyl)-ethyl]-(3-oxo-3-phenyl-propyl)-carbamic acid methyl esterHCID 178418750HCID 178418750, compound

Product 1

HCID 581091475-{[(S)-1-(4-Chloro-phenyl)-ethyl]-methoxycarbonyl-amino}-3-hydroxy-3-phenyl-pentanoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Et2Zn (1 M in hexane, 55 mL) was added dropwise to [(S)-1-(4-chloro-phenyl)-ethyl]-(3-oxo-3-phenyl-propyl)-carbamic acid methyl ester (3.80 g) dissolved in 1,2-dichloroethane (30 mL) and chilled to 0° C. under argon atmosphere. Then, (Ph3P)3RhCl (0.50 g) was added followed by the dropwise addition of methyl bromoacetate (1.0 mL) dissolved in 1,2-dichloroethane (10 mL). The resulting solution was stirred at 0-5° C. for 1 h and at ambient temperature for another 1.5 h. The solution was poured into ice-cold half-saturated aqueous NH4Cl solution (150 mL). After addition of dichloromethane, the mixture was filtered through Celite and was extracted with an additional portion of dichloromethane. The organic phase was separated and washed with water and dried (MgSO4). The solvent was removed and the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 85:15->70:30) to give the title compound as a mixture of two diastereomers.

Workup

  1. filtrationthe mixture was filtered through Celite
  2. extractionwas extracted with an additional portion of dichloromethane
  3. customThe organic phase was separated
  4. washwashed with water
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed
  7. customthe residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 85:15->70:30)

Sources & evidence

ORD record
ord-b0ce6acdc5b342d695bd7c5674dc1251
Source dataset
uspto-grants-2014_01
Patent number
US08637505B2

Reaction notes

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