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

HRID 1662525Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1662525
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

Komponenten

7

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-4bdc99621308408ba7b55af7d119adb4
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030354B2

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