反応 #1340610

ord-07800dddeecd46699471d0127fe6f142

反応方程式

[Li][CH2]CCC
Butyl lithium
CC(C)(C)OC(=O)N[C@@H]1CN(C(=O)OCc2ccccc2)CC1C=O
(3S)-1-benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-formylpyrrolidine
O=C(O)CC(O)(CC(=O)O)C(=O)O
citric acid
C=CC1CN(C(=O)OCc2ccccc2)C[C@H]1NC(=O)OC(C)(C)C
title compound
C=CC1CN(C(=O)OCc2ccccc2)C[C@H]1NC(=O)OC(C)(C)C
(3S)-1-Benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-vinylpyrrolidine

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    workup.WAITfurther at 40° C. for 5 minutes
  2. 2
    workup.STIRRINGby stirring at room temperature for 10 hours
  3. 3
    抽出The obtained aqueous layer was extracted with ethyl acetate (100 mL×2)
  4. 4
    洗浄The combined organic layer was washed sequentially by saturated sodium hydrogencarbonate (100 mL) and saturated brine (100 mL)
  5. 5
    乾燥dried over anhydrous sodium sulfate
  6. 6
    ろ過After filtration
  7. 7
    濃縮the filtrate was concentrated under reduced pressure
  8. 8
    その他The obtained residue was purified through silica gel column chromatography (ethyl acetate:n-hexane=1:4)

実験手順

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%).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08455482B2uspto-grants-2013_06