Reaction #1340610

Reaction equation

Butyl lithium

(3S)-1-benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-formylpyrrolidine

citric acid

→

title compound

(3S)-1-Benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-vinylpyrrolidine

Solvents

tetrahydrofuran

tetrahydrofuran

ethyl acetate

Conditions

Workup

1. 1
   workup.WAITfurther at 40° C. for 5 minutes
2. 2
   workup.STIRRINGby stirring at room temperature for 10 hours
3. 3
   ExtractionThe obtained aqueous layer was extracted with ethyl acetate (100 mL×2)
4. 4
   WashThe combined organic layer was washed sequentially by saturated sodium hydrogencarbonate (100 mL) and saturated brine (100 mL)
5. 5
   Dryingdried over anhydrous sodium sulfate
6. 6
   FiltrationAfter filtration
7. 7
   Concentrationthe filtrate was concentrated under reduced pressure
8. 8
   OtherThe obtained residue was purified through silica gel column chromatography (ethyl acetate:n-hexane=1:4)

Procedure

Butyl lithium (3.56 mL, 1.58 M, toluene solution) was added dropwise under cooling with ice to a suspension of methyltriphenylphosphonium bromide (2.15 g, 6.03 mmol) in tetrahydrofuran (20 mL), followed by stirring at room temperature for 20 minutes, and further at 40° C. for 5 minutes. Subsequently, a solution of (3S)-1-benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-formylpyrrolidine [an isomer mixture of (4S)-form:(4R)-form (1:3)] (700 mg, 2.01 mmol) in tetrahydrofuran (7.0 mL) was added under cooling with ice to the resultant mixture, followed by stirring at room temperature for 10 hours. The reaction mixture was poured to a 10% aqueous citric acid solution (20 mL), and the resultant mixture was diluted with ethyl acetate (100 mL). The obtained aqueous layer was extracted with ethyl acetate (100 mL×2). The combined organic layer was washed sequentially by saturated sodium hydrogencarbonate (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The obtained residue was purified through silica gel column chromatography (ethyl acetate:n-hexane=1:4), to thereby yield the title compound (an isomer mixture of (4S)-form and (4R)-form (1:4)) as a colorless oily substance (250 mg, 36%).

Source