Potassium Phosphate, Tribasic → HCID 178450652、化合物

HRID 1849677ノート

反応式

HRID 1849677 の反応式
Cl[C:2]1[C:3]([O:16][CH2:17][C@H:18]2[CH2:23][CH2:22][C@H:21]([CH3:24])[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:25]1(B(O)O)[CH2:27][CH2:26]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:25]1([C:2]2[C:3]([O:16][CH2:17][C@H:18]3[CH2:23][CH2:22][C@H:21]([CH3:24])[CH2:20][CH2:19]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])[CH2:27][CH2:26]1

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 178450706HCID 178450706、化合物

生成物 1

HCID 178450652HCID 178450652、化合物収率 90.4%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 22272177Toluene water溶媒

反応条件

温度
110 °C

実験手順

To a solution of tert-butyl 5-chloro-2-fluoro-4-((trans-4-methylcyclohexyl)-methoxy)-benzoate (6.48 g, 18.16 mmol) in toluene-water (40 mL, v/v 20:1) was added cyclopropylboronic acid (2.34 g, 27.26 mmol) and tribasic potassium phosphate (17.37, 81.84 mmol). The reaction mixture was sparged with argon for 10 minutes and then charged with tricyclohexylphosphine tetrafluoroborate (1.35 g, 3.67 mmol) and palladium acetate (0.41 g, 1.82 mmol). The mixture was heated at 110° C. for 72 hours, then cooled to ambient temperature; filtered through a pad of diatomaceous earth and washed with ethyl acetate. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (0% to 10% ethyl acetate) to give the title compound (5.95 g, 90%): 1H NMR (300 MHz, CDCl3) δ 7.37 (d, J=8.4 Hz, 1H), 6.50 (d, J=12.8 Hz, 1H), 3.78 (d, J=6.1 Hz, 2H), 1.91-1.70 (m, 8H), 1.56 (s, 9H), 1.41-129 (m, 2H), 1.14-0.95 (m, 6H), 0.65-0.60 (m, 2H).

後処理

  1. customThe reaction mixture was sparged with argon for 10 minutes
  2. temperaturecooled to ambient temperature
  3. filtrationfiltered through a pad of diatomaceous earth
  4. washwashed with ethyl acetate
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by column chromatography (0% to 10% ethyl acetate)

出典と根拠

ORDレコード
ord-ab9be3793d3f4007afc95de0f1e86e19
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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