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

(3S,4S)-3-Aminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine (1.10 g) was dissolved in methanol (13 mL). To this solution, molecular sieve 4A (440 mg) and then benzaldehyde (0.44 mL) were added. The mixture was stirred at room temperature for 1 hour, followed by addition of a borane/pyridine complex (0.44 mL) and further stirring at room temperature for 3.5 hours. Subsequently, 6 mol/L hydrochloric acid (7.3 mL) was added and the mixture was stirred at room temperature for 1 hour. A 30% aqueous solution of sodium hydroxide was then added to make the mixture basic. The mixture was extracted with diethyl ether (2×100 mL). The diethyl ether layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: hexane: ethyl acetate=4:1->1:1) to give (3S,4S)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine as a colorless tar (1.18 g).

1. additionfollowed by addition of a borane/pyridine complex (0.44 mL)
2. stirringfurther stirring at room temperature for 3.5 hours
3. stirringthe mixture was stirred at room temperature for 1 hour
4. extractionThe mixture was extracted with diethyl ether (2×100 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by silica gel column chromatography (eluant: hexane: ethyl acetate=4:1->1:1)

ORD record

ord-5b7aa62c16a64e129d2c9a36241af692

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07514451B2