4,4-Difluoro-1-methylcyclohexan-1-ol → 1-Bromo-5-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluorobenzene

HRID 1849602ノート

反応式

HRID 1849602 の反応式
ClC(Cl)(Cl)C(=N)O[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([Br:13])=[CH:8][C:7]=1[Cl:14].[F:18][C:19]1([F:27])[CH2:24][CH2:23][C:22]([CH3:26])([OH:25])[CH2:21][CH2:20]1>C(Cl)Cl.C1CCCCC1.FC(F)(F)S(O)(=O)=O>[Br:13][C:9]1[CH:8]=[C:7]([Cl:14])[C:6]([CH2:5][O:25][C:22]2([CH3:26])[CH2:23][CH2:24][C:19]([F:27])([F:18])[CH2:20][CH2:21]2)=[CH:11][C:10]=1[F:12]

参加物

6

反応物 2

HCID 666026184,4-Difluoro-1-methylcyclohexan-1-olHCID 867028534-Bromo-2-chloro-5-fluorobenzyl 2,2,2-trichloroacetimidate

生成物 1

HCID 867034571-Bromo-5-chloro-4-(((4,4-difluoro-1-methylcyclohexyl)-oxy)methyl)-2-fluorobenzene収率 18.1%

試薬・触媒・溶媒 3

HCID 62406Trifluoromethanesulfonic acid触媒HCID 6344Dichloromethane溶媒HCID 8078Cyclohexane溶媒

実験手順

To a solution of 4-bromo-2-chloro-5-fluorobenzyl 2,2,2-trichloroacetimidate (4.00 g, 10.40 mmol) and 4,4-difluoro-1-methylcyclohexanol (1.21 g, 8.05 mmol) in methylene chloride (50 mL) and cyclohexane (25 mL) was added trifluoromethanesulfonic acid (0.1 mL, 0.14 mmol) at 0 ?C. The reaction mixture was stirred for 56 hours at ambient temperature and quenched by addition of saturated sodium bicarbonate solution (10 mL), and then diluted with methylene chloride (100 mL). The organic layer was separated and washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) and recrystallization from methanol afforded the title compound (0.54 g, 17%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 7.51 (d, J=6.0 Hz, 1H), 7.30 (d, J=9.3 Hz, 1H), 4.37 (s, 2H), 2.11-1.86 (m, 6H), 1.72-1.59 (m, 2H), 1.26 (s, 3H).

後処理

  1. customquenched by addition of saturated sodium bicarbonate solution (10 mL)
  2. additiondiluted with methylene chloride (100 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue
  8. customby column chromatography (5% ethyl acetate in hexanes) and recrystallization from methanol

出典と根拠

ORDレコード
ord-746fd5b2a4b54983a61ed4921830cb89
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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