Hydrochloric Acid → Methyl 2-(2,4-difluorobenzyl)isonicotinate

HRID 1963321노트

반응식

HRID 1963321 반응식
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Cl-].[F:13][C:14]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:15]=1[CH2:16][Zn+].Cl>C1COCC1.CC(OC)(C)C.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]=[C:20]([F:22])[CH:19]=[CH:18][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

7

반응물 3

HCID 313Hydrochloric AcidHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 178505769HCID 178505769, 화합물

생성물 1

HCID 66731542Methyl 2-(2,4-difluorobenzyl)isonicotinate수율 88%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매HCID 15413tert-Butyl methyl ether용매

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온도
60 °C

실험 절차

Methyl 2-chloroisonicotinate (5.2 g, 30.31 mmol) and Pd(PPh3)4 (0.700 g, 0.61 mmol) were dissolved in THF (100 mL) under nitrogen and (2,4-difluorobenzyl)zinc(II) chloride (0.5 M in THF, 90 mL, 45.00 mmol) was added and the brown solution was stirred at 60° C. overnight (18 h). The reaction was quenched by addition of methanol (50.0 mL). The solution was diluted with EtOAc and washed with NH4Cl (aq) and brine and dried over Na2SO4 to give a red oil. The crude was redissolved in MTBE (200 mL) and solids were filtered off. Hydrogen chloride (4 M in dioxane, 7.58 mL, 30.31 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at room temperature for 15 min. The solid was collected by filtration and washed with MTBE. The solid was dissolved in MTBE/satd NaHCO3. The phases were separated, the organic phase dried over Na2SO4, filtered and evaporated to yield methyl 2-(2,4-difluorobenzyl)isonicotinate (7.011 g, 88%) as a red oil. 1H NMR (400 MHz, cdcl3) δ 3.93 (s, 3H), 4.20 (s, 2H), 6.77-6.88 (m, 2H), 7.18-7.25 (m, 1H), 7.62-7.73 (m, 2H), 8.69 (dd, 1H). MS m/z 264 (M+H)+

후처리

  1. customThe reaction was quenched by addition of methanol (50.0 mL)
  2. additionThe solution was diluted with EtOAc
  3. washwashed with NH4Cl (aq) and brine
  4. dry with materialdried over Na2SO4
  5. customto give a red oil
  6. filtrationsolids were filtered off
  7. stirringduring stirring
  8. customa suspension was formed
  9. stirringThe suspension was stirred at room temperature for 15 min
  10. filtrationThe solid was collected by filtration
  11. washwashed with MTBE
  12. dissolutionThe solid was dissolved in MTBE/satd NaHCO3
  13. customThe phases were separated
  14. dry with materialthe organic phase dried over Na2SO4
  15. filtrationfiltered
  16. customevaporated

출처 및 근거

ORD 기록
ord-776a694fab324a369f648519381e7f51
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415378B2

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