2,6-Di-tert-butyl-4-methylphenol → (1S,2S)-2-(4-{(R)-4-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-5-trifluoromethyl-indan-1-yloxy}-phenyl)-cyclopropanecarboxylic acid ethyl ester

HRID 471461노트

반응식

HRID 471461 반응식
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20](Br)[C:21]([C:25]([F:28])([F:27])[F:26])=[CH:22][CH:23]=3)[CH2:18][CH2:17]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2].[C:30]([Si:34]([CH3:46])([CH3:45])[O:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)([CH3:33])([CH3:32])[CH3:31].C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.O.[Cl-].[NH4+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([C:39]4[CH:40]=[CH:41][C:36]([O:35][Si:34]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:45])[CH3:46])=[CH:37][CH:38]=4)[C:21]([C:25]([F:28])([F:27])[F:26])=[CH:22][CH:23]=3)[CH2:18][CH2:17]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2]

참가 물질

9

반응물 4

HCID 314042,6-Di-tert-butyl-4-methylphenolHCID 75806TricyclohexylphosphineHCID 111078154-(tert-Butyldimethylsilyloxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 86703893(1S,2S)-2-[4-((R)-4-Bromo-5-trifluoromethyl-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester

생성물 1

HCID 86703892(1S,2S)-2-(4-{(R)-4-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-5-trifluoromethyl-indan-1-yloxy}-phenyl)-cyclopropanecarboxylic acid ethyl ester수율 35.1%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 25517Ammonium Chloride용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

(1S,2S)-2-[4-((R)-4-Bromo-5-trifluoromethyl-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester (200 mg, 0.43 mmol), 4-(tertbutyldimethylsilyloxy)phenylboronic acid (118 mg, 0.47 mmol) potassium carbonate (176 mg, 1.28 mmol), 2,6-di-tert-butyl-4-methylphenol (47 mg, 0.21 mmol), tricyclohexylphosphine (10 mg, 0.03 mmol), and Pd2(dba)3 (16 mg, 0.02 mmol) are suspended in a mixture of dioxane (1.7 mL) and water (0.6 mL) in a sealed tube and heated at 110° C. for 4 hours. The mixture is diluted with saturated ammonium chloride solution and extracted with ethyl acetate. The organic phase is dried and concentrated under vacuum. The residue is purified by flash chromatography (eluent: 0-30% EtOAc in cyclohexane) to give the title compound (Yield 90 mg)

후처리

  1. extractionextracted with ethyl acetate
  2. customThe organic phase is dried
  3. concentrationconcentrated under vacuum
  4. customThe residue is purified by flash chromatography (eluent: 0-30% EtOAc in cyclohexane)

출처 및 근거

ORD 기록
ord-5729f19259d845fea7812d12de707552
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633182B2

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