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 2046572노트

반응식

HRID 2046572 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-c01c39b4db9942cb91a60592103298c6
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08592426B2

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