Potassium Phosphate, Tribasic → Tert-butyl 5-cyclopropyl-2-fluoro-4-((1-(trifluoromethyl)cyclohexyl)methoxy)benzoate

HRID 1849595ノート

反応式

HRID 1849595 の反応式
Cl[C:2]1[C:3]([O:16][CH2:17][C:18]2([C:24]([F:27])([F:26])[F:25])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:28]1(B(O)O)[CH2:30][CH2:29]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:28]1([C:2]2[C:3]([O:16][CH2:17][C:18]3([C:24]([F:25])([F:26])[F:27])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]3)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:30][CH2:29]1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703448Tert-butyl 5-chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclohexyl)methoxy)benzoate

生成物 1

HCID 86703449Tert-butyl 5-cyclopropyl-2-fluoro-4-((1-(trifluoromethyl)cyclohexyl)methoxy)benzoate収率 83.6%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒2 回HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

To a mixture of tert-butyl 5-chloro-2-fluoro-4-((1-(trifluoromethyl)cyclohexyl)-methoxy)benzoate (4.37 g, 10.63 mmol), cyclopropylboronic acid (1.37 g, 15.93 mmol), potassium phosphate (10.15 g, 47.81 mmol) and tricyclohexylphosphine tetrafluoroborate (0.39 g, 1.06 mmol) in toluene (60 mL) and water (3 mL) under a nitrogen atmosphere was added palladium acetate (0.12 g, 0.53 mmol). The reaction mixture was heated at 100° C. for 18 hours and then cooled to ambient temperature. Water (20 mL) was added and the mixture, and extracted with ethyl acetate, the combined organic extracts was washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) afforded the title compound (3.70 g, 83%): 1H NMR (300 MHz, CDCl3) δ 7.40 (d, J=8.4 Hz, 1H), 6.51 (d, J=12.3 Hz, 1H), 4.07 (s, 2H), 1.99-1.88 (m, 4H), 1.76-1.62 (m, 5H), 1.55 (s, 9H), 1.48-1.24 (m, 2H), 0.91-0.82 (m, 2H), 0.62-0.55 (m, 2H).

後処理

  1. temperaturecooled to ambient temperature
  2. extractionthe mixture, and extracted with ethyl acetate
  3. washthe combined organic extracts was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by column chromatography (5% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-e5841c3505d34389ba7c1cfc1df26274
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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