Sodium Hydroxide → (rac)-Propionic acid 4-(3-fluoro-4-trifluoromethyl-phenyl)-6,7-dihydro-5H-[2]pyrindin-7-yl ester

HRID 714100ノート

反応式

HRID 714100 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:12]2[C:13]3[CH2:20][CH2:19][CH:18]([OH:21])[C:14]=3[CH:15]=[N:16][CH:17]=2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].C(N(CC)C(C)C)(C)C.[C:31](Cl)(=[O:34])[CH2:32][CH3:33].[OH-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:12]2[C:13]3[CH2:20][CH2:19][CH:18]([O:21][C:31](=[O:34])[CH2:32][CH3:33])[C:14]=3[CH:15]=[N:16][CH:17]=2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9]

参加物

6

反応物 4

HCID 14798Sodium HydroxideHCID 62324Propionyl chloride2 回HCID 81531DiisopropylethylamineHCID 718115334-[3-Fluoro-4-(trifluoromethyl)phenyl]-6,7-dihydro-5H-cyclopenta[c]pyridine-7-ol

生成物 1

HCID 71811526(rac)-Propionic acid 4-(3-fluoro-4-trifluoromethyl-phenyl)-6,7-dihydro-5H-[2]pyrindin-7-yl ester収率 11.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of (rac)-4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-ol (example 82) (24 mg, 0.081 mmol) and N,N-diisopropylethylamine (0.028 mL, 0.162 mmol) in DMF (0.2 mL) was treated with propionyl chloride (0.021 mL, 0.243 mmol) and the reaction mixture stirred at room temperature. After 15 h, another aliquot of propionyl chloride (0.021 mL, 0.243 mmol) was added, the temperature increased to 50° C. and stirring continued for 2 h. The crude reaction mixture was poured into a 1 M solution of sodium hydroxide (10 mL) and extracted with ethyl acetate (2×15 mL). The combined organic extracts were washed with a sat. solution of sodium chloride (10 mL), dried (Na2SO4), and concentrated under reduced pressure. Purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 3.2 mg (11%) of the title compound as a light brown solid. MS: 354.5 (M+H)+.

後処理

  1. temperaturethe temperature increased to 50° C.
  2. stirringstirring
  3. waitcontinued for 2 h
  4. customThe crude reaction mixture
  5. extractionextracted with ethyl acetate (2×15 mL)
  6. washThe combined organic extracts were washed with a sat. solution of sodium chloride (10 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customPurification by preparative HPLC on reversed phase
  10. washeluting with a gradient of acetonitrile/water

出典と根拠

ORDレコード
ord-86b095acfd514ba08bf49c02046d5a53
出典データセット
uspto-grants-2015_11
特許番号
US09187429B2

反応ノート

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