Potassium Phosphate, Tribasic → Methyl 3-(5,5-dimethyl-1-cyclopenten-1-yl)-5-fluoro-4-(((4-(methyloxy)phenyl)methyl)oxy)benzoate

HRID 1662440Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1662440
Br[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([F:22])[C:11]=1[O:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:5]([O:7][CH3:8])=[O:6].COC1C=CC=C(OC)[C:30]=1[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:36]=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(B2OC(C)(C)C(C)(C)O2)=CCC1>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:32][C:31]1([CH3:30])[C:36]([C:2]2[CH:3]=[C:4]([CH:9]=[C:10]([F:22])[C:11]=2[O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:35][CH2:34][CH2:33]1

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 574675872-(5,5-Dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 57467636Methyl 3-bromo-5-fluoro-4-((4-methoxybenzyl)oxy)benzoate

Produkt 1

HCID 57706615Methyl 3-(5,5-dimethyl-1-cyclopenten-1-yl)-5-fluoro-4-(((4-(methyloxy)phenyl)methyl)oxy)benzoateAusbeute 331,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A stirred mixture of 66.49C (1.63 g, 4.420 mmol), ground S-Phos (0.36 g, 0.88 mmol), palladium acetate (0.10 g, 0.45 mmol), and potassium phosphate tribasic (2.35 g, 11.06 mmol) in DMF (13 mL) and water (0.4 mL) was purged with argon and placed under vacuum and the process repeated three times. Before heating, 2-(5,5-dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (66.6C) (1.47 g, 6.63 mmol) was added via syringe and then the mixture was heated to 75° C. After 18 hours, the reaction was cooled to room temperature, diluted with water, and extracted three times with EtOAc. The organic layers were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified on a 40 g column of silica gel (0-10% EtOAc in hexanes) to afford 66.49D as a white solid (1.12 g, 66% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.69 (1H, dd, J=11.7, 2.3 Hz), 7.57 (1H, dd, J=2.0, 1.2 Hz), 7.31 (2H, m), 6.88 (2H, m), 5.56 (1H, t, J=2.5 Hz), 5.01 (2H, s), 3.91 (3H, s), 3.82 (3H, s), 2.42 (2H, td, J=7.0, 2.7 Hz), 1.86 (2H, t, J=7.2 Hz), 1.06 (6H, s).

Aufarbeitung

  1. customwas purged with argon
  2. temperatureBefore heating
  3. temperaturethe reaction was cooled to room temperature
  4. extractionextracted three times with EtOAc
  5. washwashed twice with brine
  6. dry with materialAfter drying over anhydrous sodium sulfate and filtration
  7. customthe organic solvent was removed under reduced pressure
  8. customThe residue was purified on a 40 g column of silica gel (0-10% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-25d6932f7e5f48aebd407ff3e59e1611
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030354B2

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