Carbon tetrabromide → (3R,4S)-3-azidomethyl-1-benzyloxycarbonyl-4-hydroxypyrrolidine

HRID 2108791Notes

Reaction equation

HRID 2108791 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@@H:14]([OH:16])[C@@H:13]([CH2:17]O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:19]=[N+:20]=[N-:21].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br>ClCCl.CO.CN(C)C=O>[N:19]([CH2:17][C@@H:13]1[C@H:14]([OH:16])[CH2:15][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12]1)=[N+:20]=[N-:21]

Participants

8

Reactant 4

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 66704867(3R,4S)-[1-benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol

Product 1

HCID 86600239(3R,4S)-3-azidomethyl-1-benzyloxycarbonyl-4-hydroxypyrrolidineYield 85.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(3R,4S)-[1-Benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol (2.33 g), sodium azide (1.81 g), triphenylphosphine (2.67 g) and N,N-dimethylformamide (46 mL) were mixed together. While the mixture was chilled in an ice water bath, carbon tetrabromide (3.38 g) in dichloromethane (10 mL) was added dropwise. The reaction mixture was stirred at room temperature for 13 hours and then at 60° C. for 3 hours. Subsequently, methanol (3 mL) was added and the mixture was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (200 mL) and the solution was washed with saturated brine (2×50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: ethyl acetate: hexane=2:1) to give (3R,4S)-3-azidomethyl-1-benzyloxycarbonyl-4-hydroxypyrrolidine as a milky white syrup (2.18 g).

Workup

  1. temperatureWhile the mixture was chilled in an ice water bath
  2. waitat 60° C. for 3 hours
  3. concentrationthe mixture was concentrated under reduced pressure
  4. dissolutionThe resulting residue was dissolved in ethyl acetate (200 mL)
  5. washthe solution was washed with saturated brine (2×50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (eluant: ethyl acetate: hexane=2:1)

Sources & evidence

ORD record
ord-dbf8ea1099d64e9b9678f45aca39d9c1
Source dataset
uspto-grants-2009_04
Patent number
US07514451B2

Reaction notes

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