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1,2-Dimethoxyethane → [3-(2-methyl-2H-pyrazol-3-yl)-4-trifluoromethoxy-phenyl]-carbamic acid tert-butyl ester

HRID 407498
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HRID 407498 반응식
[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[C:10](Br)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:21][N:22]1[C:26](B(O)O)=[CH:25][CH:24]=[N:23]1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>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.O>[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[C:10]([C:26]2[N:22]([CH3:21])[N:23]=[CH:24][CH:25]=2)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2]
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7

반응물 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 11182610(1-methyl-1H-pyrazol-5-yl)boronic acidHCID 59822358(3-Bromo-4-trifluoromethoxy-phenyl)-carbamic acid tert-butyl ester

생성물 1

HCID 69494845[3-(2-methyl-2H-pyrazol-3-yl)-4-trifluoromethoxy-phenyl]-carbamic acid tert-butyl ester수율 36.5%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매
HCID 962Water용매

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온도
80 °C

실험 절차

A 25-mL round-bottom flask was charged with (3-bromo-4-trifluoromethoxy-phenyl)-carbamic acid tert-butyl ester (230.0 mg, 0.65 mmol), 1-methyl pyrazole-5-boronic acid (392.9 mg, 1.93 mmol), sodium carbonate (137.8 mg, 1.3 mmol), DME (5 mL) and water (0.5 mL) under argon atmosphere. Tetrakis(triphenylphosphine)palladium (75.1 mg, 0.065 mmol) was added and reaction mixture purged with argon again. The reaction mixture was heated at 80° C. overnight then cooled to room temperature. Ethyl acetate (10 mL) was added then washed with brine and water. Organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give a residue that was subjected to a purification by flash chromatography (SiO2, Hexanes/EtOAc gradient elution) to afford [3-(2-methyl-2H-pyrazol-3-yl)-4-trifluoromethoxy-phenyl]-carbamic acid tert-butyl ester as an off-white solid in 36.5% yield. LCMS m/z (%)=358 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ: 9.83 (bs, 1H), 7.77 (d, J=8.95 Hz, 1H), 7.69 (s, 1H), 7.63 (s, 1H), 7.57 (d, J=8.84 Hz, 1H), 6.45 (s, 1H), 3.78 (s, 3H), 1.60 (s, 9H).

후처리

  1. customreaction mixture
  2. custompurged with argon again
  3. temperaturethen cooled to room temperature
  4. additionEthyl acetate (10 mL) was added
  5. washthen washed with brine and water
  6. customOrganic layer was separated
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a residue that
  11. customwas subjected to a purification by flash chromatography (SiO2, Hexanes/EtOAc gradient elution)

출처 및 근거

ORD 기록
ord-4da79938f1c24f6fb42f61deca5823f1
출처 데이터셋
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08754238B2

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