(2,3-Dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol → (+)-alpha-(2,3-Dimethoxyphenyl)-1-(2-(4-fluorophenyl)ethyl)-4-piperidinemethanol

HRID 2055854

反応式

HRID 2055854 の反応式
[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[CH:11]([CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH2:15][CH2:14]1)[OH:12]>C(OC)(C)(C)C>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C@@H:11]([CH:13]1[CH2:14][CH2:15][N:16]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH2:17][CH2:18]1)[OH:12]

参加物

3

反応物 1

HCID 60858(2,3-Dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol

生成物 1

HCID 5311271(+)-alpha-(2,3-Dimethoxyphenyl)-1-(2-(4-fluorophenyl)ethyl)-4-piperidinemethanol

試薬・触媒・溶媒 1

HCID 15413tert-Butyl methyl ether溶媒

反応条件

温度
45 °C

実験手順

To a solution of α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, butyrate ester (5a) (2.77 g, 6.2 mmol) in t-BuOMe (10 mL), Baker silica (8.3 g, 40 μ) was added. After evaporation of the ether, the silica was transferred to 180 mL of 0.1M phosphate buffer (pH 7.0) and then 25 mL of the partially purified lipase (100 g crude=230 mL of a solution) was added. The suspension was stirred at 45° C. for 4 days. The reaction was stopped by filtering the reaction mixture. Both filtrate and silica were extracted with ethyl acetate (300 mL). The organic layer was dried over MgSO4, evaporated under vacuum to give a residue, which was purified by column chromatography (60 g Baker silica (40 μ); EtOAc/heptane=3:1). (Rf0.45 for (S)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, butyrate ester (5b) and 0.06 for (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (3)). After the ester was eluted, the eluant was changed to MeOH/EtOAc=3:7 to recover (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (3) as a yellow oil (1.08 g, 46%, 98% ee). Recrystallization twice from EtOAc/heptane gave (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (3) as a white crystalline compound (770 mg, 33%, 99% ee); m.p.=114-116° C.; [α]D=14.3 (c=1; CHCl3).

後処理

  1. customAfter evaporation of the ether
  2. addition25 mL of the partially purified lipase (100 g crude=230 mL of a solution) was added
  3. filtrationby filtering the reaction mixture
  4. extractionBoth filtrate and silica were extracted with ethyl acetate (300 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. customevaporated under vacuum
  7. customto give a residue, which
  8. customwas purified by column chromatography (60 g Baker silica (40 μ); EtOAc/heptane=3:1)
  9. washAfter the ester was eluted
  10. customto recover (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (3) as a yellow oil (1.08 g, 46%, 98% ee)
  11. customRecrystallization twice from EtOAc/heptane

出典と根拠

ORDレコード
ord-f4a2cf4b7504403b92e419cf1595d635
出典データセット
uspto-grants-2008_02
特許番号
US07332607B2

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