Potassium Carbonate → Methyl 5'-(difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl-4-carboxylate

HRID 1662525노트

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HRID 1662525 반응식
C1([C@H](C2C=CC=C([O:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20](C4C=C(OC)C=CC=4F)=[C:19]([C@@H:32]4[CH2:36][CH2:35][CH2:34][C:33]4([CH3:38])[CH3:37])[CH:18]=3)C=2)CC(O)=O)CC1.[C:39](=O)([O-])[O-:40].[K+].[K+].[F:45][CH:46]([F:63])[C:47]1[CH:48]=[CH:49][C:50]([F:62])=[C:51](B2OC(C)(C)C(C)(C)O2)[CH:52]=1>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:63][CH:46]([F:45])[C:47]1[CH:48]=[CH:49][C:50]([F:62])=[C:51]([C:20]2[CH:21]=[CH:22][C:17]([C:16]([O:40][CH3:39])=[O:15])=[CH:18][C:19]=2[C:32]2[C:33]([CH3:38])([CH3:37])[CH2:34][CH2:35][CH:36]=2)[CH:52]=1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 574676372-(5-(Difluoromethyl)-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 57706097(3r)-3-Cyclopropyl-3-(3-(((2-((1r)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)phenyl)propanoic acid

생성물 1

HCID 57705519Methyl 5'-(difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl-4-carboxylate수율 90%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To a stirred solution of 66.6 I (1.12 g, 2.96 mmol) in DMF (10 mL) at 23° C. was added potassium carbonate (1.23 g, 8.87 mmol) followed by tetrakis(triphenylphosphine)palladium (0.34 g, 0.29 mmol). The mixture was purged three times with argon and placed under vacuum three times. Before heating, 83.3A (1.60 g, 5.89 mmol) was added via syringe, and then the mixture was heated to 90° C. After 19 hours, the mixture was cooled to room temperature and then diluted with water. After extracting three times with EtOAc, the mixture was concentrated in vacuo and then purified on silica gel (0%-10% EtOAc/hexane) to give 83.3B as a clear oil (0.99, 90%). 1H NMR (400 MHz, CDCl3) δ ppm 8.00 (1H, dd, J=8.0, 1.8 Hz), 7.94 (1H, d, J=1.6 Hz), 7.50 (3H, m), 7.16 (1H, t, J=9.0 Hz), 6.63 (1H, t), 5.53 (1H, s), 3.96 (3H, s), 2.25 (2H, td, J=7.0, 2.3 Hz), 1.65 (2H, t, J=7.0 Hz), 0.85 (6H, s).

후처리

  1. customThe mixture was purged three times with argon
  2. temperatureBefore heating
  3. temperaturethe mixture was cooled to room temperature
  4. extractionAfter extracting three times with EtOAc
  5. concentrationthe mixture was concentrated in vacuo
  6. custompurified on silica gel (0%-10% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-4bdc99621308408ba7b55af7d119adb4
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030354B2

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