Potassium Carbonate → 1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid (rac)-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-indan-1-yl}-amide

HRID 2046572ノート

反応式

HRID 2046572 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH:14]([NH:18][C:19]([C:21]2([NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])[CH2:23][CH2:22]2)=[O:20])[CH2:13][CH2:12]3)O1.Br[C:33]1[CH:38]=[C:37]([Cl:39])[CH:36]=[C:35]([Cl:40])[C:34]=1[O:41][CH2:42][CH:43]([F:45])[F:44].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:40][C:35]1[C:34]([O:41][CH2:42][CH:43]([F:44])[F:45])=[C:33]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH:14]([NH:18][C:19]([C:21]2([NH:24][C:25](=[O:30])[C:26]([F:27])([F:29])[F:28])[CH2:22][CH2:23]2)=[O:20])[CH2:13][CH2:12]3)[CH:38]=[C:37]([Cl:39])[CH:36]=1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 441966871-Bromo-3,5-dichloro-2-(2,2-difluoroethoxy)benzeneHCID 893916181-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid [(rac)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yl]-amide

生成物 1

HCID 601420251-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid (rac)-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-indan-1-yl}-amide収率 56%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid[(rac)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yl]-amide (intermediate A-1) (0.22 g, 502 μmol), 1-bromo-3,5-dichloro-2-(2,2-difluoro-ethoxy)-benzene (intermediate B-1) (169 mg, 552 μmol) and tri-o-tolylphosphine (30.6 mg, 100 μmol, eq: 0.2) were dissolved in THF (10.0 ml); then palladium(II)acetate (5.64 mg, 25.1 μmol, eq: 0.05) was added, followed by potassium carbonate (173 mg, 1.25 mmol), dissolved in water (1.0 ml). The reaction mixture was stirred at RT over night, then poured into H2O (50 ml) and extracted with EtOAc (2×25 mL). The organic layers were dried over MgSO4, filtered and concentrated in vacuo to give a crude product (0.377 g) which was purified by flash chromatography (silica gel, 20 g, 10% to 50% EtOAc in heptane) to yield the title compound (0.15 g, 56%) as light yellow amorphous solid. MS: 535.1 (M−H−, 2Cl).

後処理

  1. extractionextracted with EtOAc (2×25 mL)
  2. dry with materialThe organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a crude product (0.377 g) which
  6. customwas purified by flash chromatography (silica gel, 20 g, 10% to 50% EtOAc in heptane)

出典と根拠

ORDレコード
ord-c01c39b4db9942cb91a60592103298c6
出典データセット
uspto-grants-2013_11
特許番号
US08592426B2

反応ノート

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