Water → rac-4-{[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-benzoic acid ethyl ester

HRID 909059Notes

Reaction equation

HRID 909059 reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[C:4]([CH:8]2[CH2:12][NH:11][CH:10]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:9]2([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[F:27])[C:18]#[N:19])[CH:5]=[CH:6][CH:7]=1.[CH2:29]([O:31][C:32](=[O:42])[C:33]1[CH:38]=[CH:37][C:36]([N:39]=[C:40]=[O:41])=[CH:35][CH:34]=1)[CH3:30].C(N(CC)CC)C.O>ClCCl>[CH2:29]([O:31][C:32](=[O:42])[C:33]1[CH:38]=[CH:37][C:36]([NH:39][C:40]([N:11]2[CH2:12][C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:28])[C@:9]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[F:27])([C:18]#[N:19])[C@@H:10]2[CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:41])=[CH:35][CH:34]=1)[CH3:30]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 589805Ethyl 4-isocyanatobenzoateHCID 67095302rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-2-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

Product 1

HCID 51355586rac-4-{[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-benzoic acid ethyl esterYield 92.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-2-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile prepared in Example 3 (0.44 g, 1.04 mmol) in dichloromethane (5 mL) was added 4-isocyanato-benzoic acid ethyl ester (Aldrich, 0.22 g, 1.14 mmol) and triethylamine (0.22 mL, 1.56 mmol). The reaction mixture was stirred at room temperature for 30 min. Water was added, the mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (25% EtOAc in hexanes) to give rac-4-{[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-benzoic acid ethyl ester as a white solid (0.59 g, 92%)

Workup

  1. customthe mixture was partitioned between ethyl acetate and water
  2. customThe organic layer was separated
  3. washwashed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-dac20e01b292450fb6995f1478bb4efb
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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