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

HRID 540614
ノート
印刷プレビュー

反応式

HRID 540614 の反応式
[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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

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

反応条件

温度
80 °C

実験手順

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-methylpyrazole-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).

後処理

  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)

出典と根拠

ORDレコード
ord-cda4476514ee4cc68502eb6be49bf9da
出典データセット
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08871797B2

反応ノート

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