Toluene → Methyl 5-cyclopropyl-6-(2,2,2-trifluoroethoxy)nicotinate

HRID 240735

반응식

HRID 240735 반응식
Br[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(=O)([O-])[O-].[Cs+].[Cs+].[C:24]1([CH3:30])C=CC=C[CH:25]=1.C1([B-](F)(F)F)CC1.[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.O>[CH3:10][O:9][C:7](=[O:8])[C:6]1[CH:11]=[C:2]([CH:30]2[CH2:24][CH2:25]2)[C:3]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:4][CH:5]=1

참가 물질

8

반응물 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 23697338Potassium cyclopropyltrifluoroborateHCID 66686828Methyl 5-bromo-6-(2,2,2-trifluoroethoxy)nicotinate

생성물 1

HCID 71294263Methyl 5-cyclopropyl-6-(2,2,2-trifluoroethoxy)nicotinate

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 11371790Bis(adamantan-1-yl)(butyl)phosphane촉매HCID 962Water용매2회

반응 조건

온도
120 °C

실험 절차

In a 50 mL two-necked flask, methyl 5-bromo-6-(2,2,2-trifluoroethoxy)nicotinate (1 g, 3.18 mmol, Eq: 1.00, CAN 1211589-51-3) and cesium carbonate (3.11 g, 9.55 mmol, Eq: 3) were combined with toluene (25 ml) and water (2.8 ml) to give a colorless solution. The reaction mixture was 3× degassed and purged with argon, then palladium(II) acetate (14.3 mg, 63.7 μmol, Eq: 0.02), potassium cyclopropyltrifluoroborate (518 mg, 3.5 mmol, Eq: 1.1) and butyldi-1-adamantylphosphine (68.5 mg, 191 μmol, Eq: 0.06) were successively added and the reaction mixture was heated to 120° C. for 5 h when TLC indicated that the reaction was complete. The mixture was cooled to rt, poured into 50 ml H2O and extracted with AcOEt (2×50 ml). The organic layers were washed with H2O/NaCl sol, combined, dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (silica gel, 70 g, 0% to 20% EtOAc in heptane) yielded eventually 836 mg of the title compound as light yellow semisolid; MS (EI) 276.0 (M+H)+.

후처리

  1. customto give a colorless solution
  2. customdegassed
  3. custompurged with argon
  4. temperatureThe mixture was cooled to rt
  5. extractionextracted with AcOEt (2×50 ml)
  6. washThe organic layers were washed with H2O/NaCl
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography (silica gel, 70 g, 0% to 20% EtOAc in heptane)

출처 및 근거

ORD 기록
ord-613fe49f866747ac96411aeb12ac172a
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648099B2

연결된 노트

불러오는 중…