Methanol → (3S,4R)-Benzyl 3-(bromomethyl)-4-hydroxypyrrolidine-1-carboxylate
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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:39].CO>CN(C)C(=O)C.ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[C@@H:13]([CH2:17][Br:39])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
(3R,4R)-(1-Benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl)methanol (503 mg) and triphenylphosphine (577 mg) were dissolved in N,N-dimethylacetamide (10 mL) While this solution was chilled in an ice water bath, carbon tetrabromide (730 mg) in dichloromethane (2 mL) was added dropwise. After the reaction mixture was stirred at room temperature for 5 hours, methanol (1 mL) was added and the mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 mL), washed with saturated brine (2×10 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (eluant: ethyl acetate: hexane=2:1) to give (3S,4R)-1-benzyloxycarbonyl-3-bromomethyl-4-hydroxypyrrolidine as a milky white syrup (503 mg).
Workup
- temperaturewas chilled in an ice water bath
- concentrationthe mixture was concentrated under reduced pressure
- dissolutionThe residue was dissolved in ethyl acetate (50 mL)
- washwashed with saturated brine (2×10 mL)
- dry with materialdried over anhydrous sodium sulfate
- concentrationconcentrated under reduced pressure
- customThe resultant residue was purified by silica gel column chromatography (eluant: ethyl acetate: hexane=2:1)
Sources & evidence
- ORD record
- ord-75482a4d1241449193a217d579dd6cde
- Source dataset
- uspto-grants-2009_04
- Patent number
- US07514451B2
Reaction notes
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