5-Bromo-2-methoxypyridine → 1-(6-Methoxypyridin-3-yl)-4-(trifluoromethyl)cyclohexanol

HRID 1669646

反応式

HRID 1669646 の反応式
C([Li])CCC.Br[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=1.[F:15][C:16]([F:25])([F:24])[CH:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1>C1COCC1>[CH3:14][O:13][C:10]1[N:11]=[CH:12][C:7]([C:20]2([OH:23])[CH2:19][CH2:18][CH:17]([C:16]([F:24])([F:25])[F:15])[CH2:22][CH2:21]2)=[CH:8][CH:9]=1

参加物

5

反応物 3

HCID 27348955-Bromo-2-methoxypyridineHCID 27774914-(Trifluoromethyl)cyclohexanoneHCID 178418339Butyllithium

生成物 1

HCID 673350851-(6-Methoxypyridin-3-yl)-4-(trifluoromethyl)cyclohexanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

n-Butyllithium (3 mL of a 2.5 M solution in hexanes, 7.5 mmol) was added dropwise to 5-bromo-2-methoxy pyridine (6.0 mmol, 0.78 mL) in 40 mL of THF cooled in a dry ice/acetone bath. After aging for 15 min, 4-trifluoromethylcyclohexanone (6.0 mmol, 1 g) was added and the reaction mixture was allowed to slowly warm to 0° C. over 2 h. The reaction was cooled in a dry ice/acetone bath and the reaction was quenched by addition of sat. ammonium chloride (aq), then saturated sodium bicarbonate (aq). The reaction mixture was extracted with hexanes/EtOAc. The organic phase was concentrated and the resultant residue was purified by flash chromatography on silica gel using a step gradient of 4:1, 2:1 and 1:1 (v/v) EtOAc/hexanes to give the title compound as a mixture of isomers. LC-MS (ESI): m/z=276.2 [M+1]+.

後処理

  1. temperaturecooled in a dry ice/acetone bath
  2. temperatureThe reaction was cooled in a dry ice/acetone bath
  3. customthe reaction was quenched by addition of sat. ammonium chloride (aq)
  4. extractionThe reaction mixture was extracted with hexanes/EtOAc
  5. concentrationThe organic phase was concentrated
  6. customthe resultant residue was purified by flash chromatography on silica gel using a step gradient of 4:1, 2:1 and 1:1 (v/v) EtOAc/hexanes

出典と根拠

ORDレコード
ord-3a86f9390fc64fbb9c926d4849ab3d1d
出典データセット
uspto-grants-2011_08
特許番号
US07989472B2

関連ノート

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