Acetamide → Methyl 5-acetamido-6-(2,2,2-trifluoroethoxy)nicotinate

HRID 623450노트

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HRID 623450 반응식
Cl[C:2]1[C:3]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[C:18]([NH2:21])(=[O:20])[CH3:19].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C(O)(C)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O>[C:18]([NH:21][C:2]1[C:3]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])(=[O:20])[CH3:19]

참가 물질

9

반응물 4

HCID 178AcetamideHCID 62657Potassium Phosphate, TribasicHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 67509641HCID 67509641, 화합물

생성물 1

HCID 67510072Methyl 5-acetamido-6-(2,2,2-trifluoroethoxy)nicotinate수율 18%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 6386tert-Butanol용매HCID 8857Ethyl Acetate용매

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온도
110 °C

실험 절차

A mixture of methyl 5-chloro-6-(2,2,2-trifluoroethoxy)nicotinate (3.08 g, 11.4 mmol, Step-1), acetamide (0.70 mL, 13.7 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.73 g, 0.80 mmol), potassium phosphate (7.27 g, 34.3 mmol) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.34 g, 0.800 mmol) in tert-butyl alcohol (114 mL) is stirred for 3 hours at 110° C. The reaction mixture is poured into water and extricated with ethyl acetate and dried over sodium sulfate and concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (3:1 to 1:1) to give 0.59 g (18% yield) of the title compound as a white solid.

후처리

  1. dry with materialdried over sodium sulfate
  2. concentrationconcentrated in vacuo
  3. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (3:1 to 1:1)

출처 및 근거

ORD 기록
ord-a0285588f61546bb85b83ffe530def13
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09302991B2

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