Benzaldehyde → (3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

A mixture (310 mg) of (3S,4R)-3-aminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine and 3-aminomethyl-1-benzyloxycarbonyl-3-pyrroline was dissolved in methanol (4 mL). To this solution, molecular sieves 4A (130 mg) and benzaldehyde (0.13 mL) were sequentially added and the mixture was stirred at room temperature for 1 hour. Subsequently, a borane-pyridine complex (0.19 mL) was added and the mixture was further stirred at room temperature for 4 hours. This was followed by addition of 6 mol/L hydrochloric acid (2 mL) and stirring at room temperature for 1 hour. Subsequently, a 30% aqueous solution of sodium hydroxide was added to make the mixture basic and the mixture was extracted with diethyl ether (3×10 mL). The diethyl ether extracts were combined and the combined diethyl ether layer was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant=dichloromethane: methanol=10:1) to give 177 mg of (3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine as a pale yellow oil.

1. additionSubsequently, a borane-pyridine complex (0.19 mL) was added
2. stirringthe mixture was further stirred at room temperature for 4 hours
3. stirringstirring at room temperature for 1 hour
4. extractionthe mixture was extracted with diethyl ether (3×10 mL)
5. concentrationthe combined diethyl ether layer was concentrated under reduced pressure
6. customThe resulting residue was purified on a silica gel column (eluant=dichloromethane: methanol=10:1)

ORD record

ord-5bc1aff3d99741a0b59de677506cec59

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07153851B2