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

HRID 2108778Notes

Reaction equation

HRID 2108778 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 66704861(3R,4R)-(1-benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl)methanol

Product 1

HCID 86600232(3R,4R)-3-azidomethyl-1-benzyloxycarbonyl-4-hydroxypyrrolidineYield 89.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Process B: (3R,4R)-[1-Benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol (3.00 g), sodium azide (2.32 g), triphenylphosphine (3.43 g) and N,N-dimethylformamide (60 mL) were mixed together. While this mixture was chilled in an ice water bath, carbon tetrabromide (4.34 g) in dichloromethane (14 mL) was added dropwise. The reaction mixture was stirred at room temperature for 25 hours and then at 60° C. for 2 hours. Subsequently, methanol (5 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,4R)-3-azidomethyl-1-benzyloxycarbonyl-4-hydroxypyrrolidine as a pale brown syrup (2.94 g).

Workup

  1. temperatureWhile this mixture was chilled in an ice water bath
  2. waitat 60° C. for 2 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-b135ceee68b04f11bf1002d09c9131b4
Source dataset
uspto-grants-2009_04
Patent number
US07514451B2

Reaction notes

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