Potassium Carbonate → Methyl 2-(3-fluoro-4-(trifluoromethyl)phenyl)isonicotinate

HRID 1963223노트

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HRID 1963223 반응식
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[K+].[K+].[F:18][C:19]1[CH:20]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:22]=[CH:23][C:24]=1[C:25]([F:28])([F:27])[F:26]>CO.Cl[Pd]Cl>[F:18][C:19]1[CH:20]=[C:21]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:22]=[CH:23][C:24]=1[C:25]([F:26])([F:27])[F:28]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 467390543-Fluoro-4-(trifluoromethyl)phenylboronic acid pinacol ester

생성물 1

HCID 66732503Methyl 2-(3-fluoro-4-(trifluoromethyl)phenyl)isonicotinate수율 76.1%

시약·촉매·용매 2

HCID 24290Palladium Chloride촉매HCID 887Methanol용매

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온도
100 °C

실험 절차

Methyl 2-chloroisonicotinate (2.86 g, 16.67 mmol), PdCl2 (dppf) (0.278 g, 0.38 mmol) and potassium carbonate (1.161 mL, 19.24 mmol) were distributed equally over 3 microwave reaction vials. 2-(3-Fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-borolane (3.72 g, 12.82 mmol) dissolved in methanol (45 mL) was split into 3 equal portions and added to the vials. The vials were capped and heated in a single node microwave reactor at 100° C. for 10 min each. The contents of the vials was combined and the solvent evaporated. The residue was dissolved in DCM and washed with water. The organic phase was filtered through a phase separator and evaporated. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column. 7:1 of heptane:EtOAc over 10 CV was used as mobile phase. Crude methyl 2-(3-fluoro-4-(trifluoromethyl)phenyl)isonicotinate (2.92 g, 76%) was isolated. MS m/z 300 (M+H)+

후처리

  1. customwas split into 3 equal portions
  2. additionadded to the vials
  3. customThe vials were capped
  4. customthe solvent evaporated
  5. dissolutionThe residue was dissolved in DCM
  6. washwashed with water
  7. filtrationThe organic phase was filtered through a phase separator
  8. customevaporated
  9. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column

출처 및 근거

ORD 기록
ord-284d82b5404541aa96bfc01eee69f6a0
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415378B2

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