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

HRID 1662525ノート

反応式

HRID 1662525 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-4bdc99621308408ba7b55af7d119adb4
出典データセット
uspto-grants-2011_10
特許番号
US08030354B2

反応ノート

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