Dichloromethane → (2S,4S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1527321Notes

Reaction equation

HRID 1527321 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:9][C@@H:8]([C:10](=[O:21])[NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=2[F:20])[N:7]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:6]1)=O.[BH4-].[Li+].C(Cl)Cl>C1COCC1.[Cl-].[Na+].O>[C:25]([O:24][C:22]([N:7]1[CH2:6][C@@H:5]([CH2:3][OH:2])[CH2:9][C@H:8]1[C:10](=[O:21])[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=1[F:20])=[O:23])([CH3:28])([CH3:26])[CH3:27]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 4148881Lithium borohydrideHCID 68284043(3S,5S)-5-(3-Chloro-2-fluoro-benzylcarbamoyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

Product 1

HCID 68283501(2S,4S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution (3S,5S)-5-(3-chloro-2-fluoro-benzylcarbamoyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (550 mg, 1.33 mmol) in THF (6 mL) was added lithium borohydride (2 M in THF, 1.46 mL, 2.92 mmol) at RT and the mixture was further stirred for 2 h under N2 atmosphere. After completion brine and CH2Cl2 were added, the layers were separated and the aqueous one re-extracted with CH2Cl2. The combined organic layers were dried (MgSO4), filtered and concentrated. The crude was purified by flash column chromatography on silica gel (eluent: EtOAc) to give the desired material. MS (LC/MS): 409.1 [M+Na]+, 287.0 [MH−Boc]+, 385.1 [M−H]−; tR (HPLC conditions f): 1.82 min.

Workup

  1. customthe layers were separated
  2. extractionthe aqueous one re-extracted with CH2Cl2
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by flash column chromatography on silica gel (eluent: EtOAc)

Sources & evidence

ORD record
ord-afd96f09b8a74490ac36b0e70e6431d4
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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