Hydrochloric Acid → Methyl 2-(2,6-difluorobenzyl)isonicotinate

HRID 1963313노트

반응식

HRID 1963313 반응식
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br-].[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:15]=1[CH2:16][Zn+].Cl>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:15]=1[CH2:16][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 178505728HCID 178505728, 화합물

생성물 1

HCID 66731334Methyl 2-(2,6-difluorobenzyl)isonicotinate수율 58.6%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매

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온도
60 °C

실험 절차

Methyl 2-chloroisonicotinate (5.600 g, 32.64 mmol) and Pd(PPh3)4 (0.754 g, 0.65 mmol) were dissolved in THF (100 mL) under nitrogen and (2,6-difluorobenzyl)zinc(II) bromide (0.5 M in THF, 100 mL, 50.00 mmol) was added and the resulting solution was stirred at 60° C. for 4 h before it was cooled to room temperature and quenched with methanol (50.0 mL). The mixture was diluted with EtOAc and washed with satd NH4Cl. The organic phase was dried with MgSO4, filtered and evaporated. The crude product was dissolved in MTBE (200 mL), solids were filtered off, and HCl (4 M in dioxane, 8.16 mL, 32.64 mmol) was added dropwise. The mixture was stirred for 10 minutes before the precipitate was filtered off, washed with MTBE and dissolved in MTBE/satd NaHCO3. The organic layer was dried with MgSO4, filtered and evaporated to give methyl 2-(2,6-difluorobenzyl)isonicotinate (5.03 g, 58.6%) as a white solid. 1H NMR (400 MHz, cdcl3) δ 3.92 (s, 3H), 4.29 (s, 2H), 6.87-6.97 (m, 2H), 7.18-7.29 (m, 1H), 7.61-7.73 (m, 2H), 8.63-8.70 (m, 1H). MS m/z 264 (M+H)+

후처리

  1. temperaturewas cooled to room temperature
  2. customquenched with methanol (50.0 mL)
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with satd NH4Cl
  5. dry with materialThe organic phase was dried with MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe crude product was dissolved in MTBE (200 mL)
  9. filtrationsolids were filtered off
  10. stirringThe mixture was stirred for 10 minutes before the precipitate
  11. filtrationwas filtered off
  12. washwashed with MTBE
  13. dissolutiondissolved in MTBE/satd NaHCO3
  14. dry with materialThe organic layer was dried with MgSO4
  15. filtrationfiltered
  16. customevaporated

출처 및 근거

ORD 기록
ord-ea9e7a8d5549486f9713f3301b3e68e2
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415378B2

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