Pivalic acid → 5-(5-chloro-2-difluoromethoxyphenyl)-4-nitro-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazole

HRID 529737

反応式

HRID 529737 の反応式
[N+:1]([C:4]1[CH:5]=[N:6][N:7]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[CH:8]=1)([O-:3])=[O:2].Br[C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[O:25][CH:26]([F:28])[F:27].C(=O)([O-])[O-].[K+].[K+].CC(C)(C)C(O)=O>CC(N(C)C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2>[Cl:24][C:22]1[CH:23]=[CH:18][C:19]([O:25][CH:26]([F:27])[F:28])=[C:20]([C:8]2[N:7]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:6]=[CH:5][C:4]=2[N+:1]([O-:3])=[O:2])[CH:21]=1

参加物

8

反応物 4

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 463115372-Bromo-4-chloro-1-(difluoromethoxy)benzeneHCID 58405687HCID 58405687、化合物

生成物 1

HCID 1238242275-(5-chloro-2-difluoromethoxyphenyl)-4-nitro-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazole収率 78%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 11371790Bis(adamantan-1-yl)(butyl)phosphane触媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
130 °C

実験手順

To a solution of 4-nitro-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazole (preparation described in WO2011003065) (46.5 g, 191 mmol) in DMA (350 mL) was added 2-bromo-4-chloro-1-difluoromethoxybenzene (64.0 g, 248 mmol), palladium (II) acetate (2.15 g, 9.6 mmol), di-(adamantyl)-n-butylphosphine (5.0 g, 13.4 mmol), potassium carbonate (79.2 g, 573 mmol) and trimethylacetic acid (5.27 g, 51.6 mmol). The mixture was degassed with nitrogen for 10 minutes then heated at 130° C. for 8 hours. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate and washed with water and brine, dried (MgSO4), filtered and evaporated. The resultant crude material was purified by flash chromatography on silica eluting with 0-10% EtOAc in cyclohexane to afford 5-(5-chloro-2-difluoromethoxyphenyl)-4-nitro-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazole (62.4 g, 78%). 1H NMR (400 MHz, CDCl3) δ: (ppm) 8.24 (s, 1H), 7.52-7.53 (m, 2H), 6.39 (t, 1H), 5.29-5.30 (m, 2H), 3.63-3.64 (m, 2H), 0.90 (s, 9H).

後処理

  1. customThe mixture was degassed with nitrogen for 10 minutes
  2. temperatureto cool to room temperature
  3. additiondiluted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe resultant crude material was purified by flash chromatography on silica eluting with 0-10% EtOAc in cyclohexane

出典と根拠

ORDレコード
ord-c2d925b977ff45c09ae164709cf9e987
出典データセット
uspto-grants-2016_05
特許番号
US09346815B2

関連ノート

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