Tricyclohexylphosphine → {5-[4-(Ethoxycarbonyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl]-3-fluoro-2-methoxyphenyl}boronic acid

HRID 1508533노트

반응식

HRID 1508533 반응식
[F:1][C:2]1[CH:3]=[C:4]([N:11]2[C:15]([C:16]([F:19])([F:18])[F:17])=[C:14]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:13]=[N:12]2)[CH:5]=[C:6](I)[C:7]=1[O:8][CH3:9].[B:25]1(B2OC(C)(C)CC(C)O2)[O:30]C(C)(C)CC(C)[O:26]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])(=O)C.[K+]>O1CCOCC1>[CH2:23]([O:22][C:20]([C:14]1[CH:13]=[N:12][N:11]([C:4]2[CH:3]=[C:2]([F:1])[C:7]([O:8][CH3:9])=[C:6]([B:25]([OH:30])[OH:26])[CH:5]=2)[C:15]=1[C:16]([F:19])([F:18])[F:17])=[O:21])[CH3:24]

참가 물질

6

반응물 4

HCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2734616Bis(hexylene Glycolato)diboronHCID 67517199Ethyl 1-(3-fluoro-5-iodo-4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

생성물 1

HCID 123962909{5-[4-(Ethoxycarbonyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl]-3-fluoro-2-methoxyphenyl}boronic acid

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

Ethyl 1-(3-fluoro-5-iodo-4-methoxyphenyl)-5-(trifluoromethyl)-1h-pyrazole-4-carboxylate (340 mg, 0.742 mmol), bis(hexyleneglycolato)diboron (283 mg, 1.113 mmol), tricyclohexylphosphine (62.4 mg, 0.223 mmol), potassium acetate (182 mg, 1.855 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (121 mg, 0.148 mmol) and 1,4-dioxane (10 mL) were sealed in a microwave vessel and subject to microwave irradiation at 140° C. for a total of 2 hrs (1+1). The crude mixture was combined with the reaction crude from an identical probe reaction (32 mg scale). Volatiles were removed under reduced pressure. The resulting crude mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge). The column was eluted by an EtOAc/hexanes mixture (0% to 40%). Related fractions were pooled and evaporated to afford a brown oil as a mixture of the titled compound and the de-iodinated reduced by-product (step B). LCMS calc.=376.09. found=377.18 (M+H)+.

후처리

  1. customVolatiles were removed under reduced pressure
  2. customThe resulting crude mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge)
  3. washThe column was eluted by an EtOAc/hexanes mixture (0% to 40%)
  4. customevaporated
  5. customto afford a brown oil

출처 및 근거

ORD 기록
ord-5b39c925d5c540f1b78ee3597ec16b68
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221834B2

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