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

HRID 1508533ノート

反応式

HRID 1508533 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-5b39c925d5c540f1b78ee3597ec16b68
出典データセット
uspto-grants-2015_12
特許番号
US09221834B2

反応ノート

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