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

HRID 1963321ノート

反応式

HRID 1963321 の反応式
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]

参加物

7

反応物 3

HCID 313Hydrochloric AcidHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 178505769HCID 178505769、化合物

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒HCID 15413tert-Butyl methyl ether溶媒

反応条件

温度
60 °C

実験手順

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)+

後処理

  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

出典と根拠

ORDレコード
ord-776a694fab324a369f648519381e7f51
出典データセット
uspto-grants-2013_04
特許番号
US08415378B2

反応ノート

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