Water → HCID 68283529, compound

HRID 1527408Notes

Reaction equation

HRID 1527408 reaction equation
C(OC(N1C[C@@H](N=[N+]=[N-])[C@H](F)[C@H]1C(=O)N[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=O)(C)(C)C.[C:27]([O:31][C:32]([N:34]1[CH2:38][C@H:37]([F:39])[C@@H:36]([N:40]=[N+]=[N-])[C@H:35]1[C:43](=[O:52])NCC1C=CC=CC=1)=[O:33])([CH3:30])([CH3:29])[CH3:28].CP(C)C.[OH2:57]>C1COCC1>[C:27]([O:31][C:32]([N:34]1[CH2:38][C@H:37]([F:39])[C@@H:36]([NH2:40])[C@H:35]1[C:43]([O:52][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:57])=[O:33])([CH3:28])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 962WaterHCID 68983TrimethylphosphineHCID 86673850HCID 86673850, compoundHCID 86673851HCID 86673851, compound

Product 1

HCID 68283529HCID 68283529, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of (2R,3R,4R)-4-azido-2-benzylcarbamoyl-3-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester and (2S,3S,4S)-3-azido-2-benzylcarbamoyl-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester (3.52 g, 8.98 mmol) (described in Scheme B22), trimethylphosphine in THF (17.97 mL, 17.97 mmol) and water (0.32 mL, 17.97 mmol) in THF (100 mL) was stirred for 16 h at RT. The reaction mixture was quenched with water and extracted twice with EtOAc. The organic phases were joined, washed with brine, dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography on silica gel (c-hexane/EtOAc 1:1) gave (2S,3S,4S)-3-amino-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester: MS (UPLC/MS): 339 [M+H]+; tR (HPLC conditions f): 1.59 min and (2R,3S,4R)-4-amino-3-fluoro-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester: MS (UPLC/MS): 339 [M+H]+; tR (HPLC conditions f): 1.62 min.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted twice with EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash column chromatography on silica gel (c-hexane/EtOAc 1:1)

Sources & evidence

ORD record
ord-b41baacf26c1418aa868688c226f747d
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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