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

HRID 529737

반응식

HRID 529737 반응식
[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

참가 물질

8

반응물 4

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 463115372-Bromo-4-chloro-1-(difluoromethoxy)benzeneHCID 58405687HCID 58405687, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 11371790Bis(adamantan-1-yl)(butyl)phosphane촉매HCID 31374Dimethylacetamide용매

반응 조건

온도
130 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c2d925b977ff45c09ae164709cf9e987
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346815B2

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