Acetic Acid → (R)-1-{5-[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamino]-2-methyl-benzyl}-pyrrolidine-3-carboxylic acid

HRID 1629726Notes

Reaction equation

HRID 1629726 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([CH3:22])=[C:18]([CH:21]=2)[CH:19]=O)[C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[CH3:23].[NH:24]1[CH2:28][CH2:27][C@@H:26]([C:29]([OH:31])=[O:30])[CH2:25]1.CC(O)=O>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([CH3:22])=[C:18]([CH:21]=2)[CH2:19][N:24]2[CH2:28][CH2:27][C@@H:26]([C:29]([OH:31])=[O:30])[CH2:25]2)[C:9]([F:11])([F:12])[F:10])=[CH:4][C:3]=1[CH3:23]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 1501970(3R)-3-Pyrrolidinecarboxylic acidHCID 866562265-[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamino]-2-methyl-benzaldehyde

Product 1

HCID 53340673(R)-1-{5-[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamino]-2-methyl-benzyl}-pyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of aldehyde INT 33 (2.50 g, 7.32 mmol) and (R)-pyrrolidine-3-carboxylic acid (0.93 g, 8.05 mmol) in MeOH (74 mL) was added HOAc (0.42 mL, 7.32 mmol) followed by PS—CNBH3 (2.5 mmol/g, 2.93 g, 7.32 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was filtered through Celite. The filtrate was concentrated. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3 and water. The aqueous layers were extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (CH2Cl2/MeOH) to afford the title compound Example 21.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. concentrationThe filtrate was concentrated
  3. washwashed with saturated aqueous NaHCO3 and water
  4. extractionThe aqueous layers were extracted with EtOAc (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-85fc6a5fcf504090b9a28880a614e43d
Source dataset
uspto-grants-2014_07
Patent number
US08791100B2

Reaction notes

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