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

HRID 404340노트

반응식

HRID 404340 반응식
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

참가 물질

8

반응물 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

생성물 1

HCID 57706615Methyl 3-(5,5-dimethyl-1-cyclopenten-1-yl)-5-fluoro-4-(((4-(methyloxy)phenyl)methyl)oxy)benzoate수율 331.1%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매2회HCID 6228Dimethylformamide용매

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온도
75 °C

실험 절차

A stirred mixture of T10.3 (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 three times with argon and placed under vacuum three times. 2-(5,5-Dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (T2.2) (1.47 g, 6.63 mmol) was added to the mixture via syringe, and the resulting mixture was heated to 75° C. After 18 hours (black solution), the reaction was cooled to room temperature, diluted with water, and extracted three times with EtOAc. The combined organic layers were 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 T10.4 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).

후처리

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

출처 및 근거

ORD 기록
ord-87d70399898c4c3a99dfc4648fe42296
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748462B2

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