Methyl 2-chloropyridine-4-carboxylate → Methyl 2-(2-fluorobenzyl)isonicotinate

HRID 1963274노트

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HRID 1963274 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]=[CH:20][CH:19]=[CH:18][C:15]=1[CH2:16][Zn+]>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]=[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

5

반응물 2

HCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 178505630HCID 178505630, 화합물

생성물 1

HCID 66732036Methyl 2-(2-fluorobenzyl)isonicotinate수율 73%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매

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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 under nitrogen in THF (100 mL) and (2-fluorobenzyl)zinc(II) chloride (0.5 M in THF) (90 mL, 45.00 mmol) was added and the brown solution was stirred at 60° C. for 18 h. The reaction was quenched by addition of methanol (50.0 mL). The solution was diluted with EtOAc, washed with NH4Cl (aq) and dried over Na2SO4, then evaporated. The compound was purified in 2 runs via Biotage, SNAP 340 g KP-SIL, eluent isocratic heptane/ethyl acetate 8:2 for 2 CV, then linear gradient heptane/ethyl acetate 8:2 to 5:5 over 5 CV to give methyl 2-(2-fluorobenzyl)isonicotinate (5.42 g, 73%) as a yellow oil. 1H NMR (400 MHz, cdcl3) 3.92 (s, 3H), 4.25 (s, 2H), 7.00-7.13 (m, 2H), 7.18-7.30 (m, 2H), 7.64-7.74 (m, 2H), 8.69 (d, 1H). MS m/z 246 (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)
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe compound was purified in 2

출처 및 근거

ORD 기록
ord-26a95452519c465d8aad1797012c31b4
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415378B2

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