Lithium Chloride → (2S,5R)-1-Benzyl-5-hydroxymethyl-pyrrolidine-2-carboxylic acid (3-trifluoromethoxy-phenyl)-amide

HRID 1527342Notes

Reaction equation

HRID 1527342 reaction equation
C([O:3][C:4]([C@H:6]1[CH2:10][CH2:9][C@@H:8]([C:11](=[O:24])[NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=2)[N:7]1[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=O)C.[Li+].[Cl-].[BH4-].[Na+]>C1COCC1.CCO>[F:22][C:20]([F:21])([F:23])[O:19][C:15]1[CH:14]=[C:13]([NH:12][C:11]([C@@H:8]2[CH2:9][CH2:10][C@H:6]([CH2:4][OH:3])[N:7]2[CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:24])[CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 4311764Sodium borohydrideHCID 68283977(2R,5S)-1-Benzyl-5-(3-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid ethyl ester

Product 1

HCID 71042580(2S,5R)-1-Benzyl-5-hydroxymethyl-pyrrolidine-2-carboxylic acid (3-trifluoromethoxy-phenyl)-amide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2R,5S)-1-benzyl-5-(3-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid ethyl ester (2.5 g, 5.73 mmol) in a mixture of THF (40 mL) and EtOH (20 mL) was added LiCl (486 mg, 11.5 mmol) followed by NaBH4 (451 mg, 11.5 mmol) and the mixture was stirred at RT overnight. The crude reaction mixture was concentrated, EtOAc and 1N HCl were added, the layers were separated and the aqueous one back-extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude residue was used without further purification in the next step. MS (LC/MS): 395 [M+H]+; tR (HPLC conditions b): 3.66 min.

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated
  3. additionEtOAc and 1N HCl were added
  4. customthe layers were separated
  5. extractionthe aqueous one back-extracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was used without further purification in the next step
  11. custom3.66 min.

Sources & evidence

ORD record
ord-e6578c0ccc8846b79c8555e756973dc3
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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