Water → (R*)-3-[1-((S)-7-Fluoro-2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-3-yl]phenol

HRID 2365979ノート

反応式

HRID 2365979 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@H:8]([CH2:11]OS(C)(=O)=O)[O:7][C:6]=2[CH:17]=1.Br.[NH:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([C:25]2[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=2)[CH2:20]1.C([O-])(O)=O.[Na+].O>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@H:8]([CH2:11][N:19]3[CH2:24][CH2:23][CH2:22][C@H:21]([C:25]4[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=4)[CH2:20]3)[O:7][C:6]=2[CH:17]=1

参加物

6

反応物 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 68490019(R*)-3-(piperidin-3-yl)phenol HBrHCID 86644722methanesulfonic acid (R)-(7-fluoro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl ester

生成物 1

HCID 25175339(R*)-3-[1-((S)-7-Fluoro-2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-3-yl]phenol収率 36.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

A mixture of methanesulfonic acid (R)-(7-fluoro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl ester (51 mg, 0.19 mmol), (R*)-3-(piperidin-3-yl)phenol HBr (50 mg, 0.19 mmol) and NaHCO3 (33 mg, 0.39 mmol) in DMF (3.5 ml) was heated at 120° C. for 1.5 h. Water (10 ml) was added to the cooled mixture, which was then extracted with EtOAc (3×10 ml). The combined organic layers were washed several times with water and finally twice with brine. Drying (Na2SO4), filtering and evaporation of the solvent gave the crude product, which was recrystallised from EtOH to afford 24 mg of the title compound as a white solid.

後処理

  1. extractionwas then extracted with EtOAc (3×10 ml)
  2. washThe combined organic layers were washed several times with water
  3. dry with materialDrying (Na2SO4)
  4. filtrationfiltering
  5. customevaporation of the solvent
  6. customgave the crude product, which
  7. customwas recrystallised from EtOH

出典と根拠

ORDレコード
ord-f8b10079841e4044a295242cd20c707a
出典データセット
uspto-grants-2014_04
特許番号
US08697723B2

反応ノート

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