1-Bromo-4-fluorobenzene → 2-(4-Fluorophenyl)-5-[(tetra-hydro-2-pyranyloxy)methyl]pyridine

HRID 372923

반응식

HRID 372923 반응식
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.Cl[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)=[CH:13][N:12]=1>CC(P(C1C=CC=CC=1)C1C=CC=CC=1)C.C1C=CC(PC2C=CC=CC=2)=CC=1.[Cl-].[Ni].O1CCCC1>[F:9][C:6]1[CH:7]=[CH:8][C:3]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)=[CH:13][N:12]=2)=[CH:4][CH:5]=1

참가 물질

6

반응물 3

HCID 99931-Bromo-4-fluorobenzeneHCID 5462224MagnesiumHCID 221273782-Chloro-5-{[(oxan-2-yl)oxy]methyl}pyridine

생성물 1

HCID 198125972-(4-Fluorophenyl)-5-[(tetra-hydro-2-pyranyloxy)methyl]pyridine수율 77.7%

시약·촉매·용매 2

HCID 21654969Diphenylphosphane;diphenyl(propan-2-yl)phosphane;nickel;chloride촉매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
3 °C

실험 절차

A grignard reagent solution prepared from 1.53 g of magnesium, 10.5 g of 1-bromo-4-fluorobenzene and 70 ml of tetrahydrofuran was added dropwise at 3°-7° C. within 45 minutes to a mixture of 16.9 g of crude 2-chloro-5-[(tetrahydro-2-pyranyloxy)methyl]pyridine, 60 ml of tetrahydrofuran and 0.62 g of 1,3-bis(diphenylphosphino)-propanenickel-(II) chloride. The dark reaction mixture was stirred at 3° C. for a further 1 hr. and at room temperature for 2 hrs. and then extracted with 200 ml of diethyl ether and 120 ml of 0.5N ammonium chloride solution. The organic phase was washed neutral with water, dried over sodium sulphate, filtered and concentrated. Chromatographic purification of the residue on 230 g of silica gel with hexane/ethyl acetate (vol. 9:1) yielded 13.4 g of 2-(4-fluorophenyl)-5-[(tetra-hydro-2-pyranyloxy)methyl]pyridine as a yellowish oil.

후처리

  1. customThe dark reaction mixture
  2. waitand at room temperature for 2 hrs
  3. extractionand then extracted with 200 ml of diethyl ether and 120 ml of 0.5N ammonium chloride solution
  4. washThe organic phase was washed neutral with water
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customChromatographic purification of the residue on 230 g of silica gel with hexane/ethyl acetate (vol. 9:1)

출처 및 근거

ORD 기록
ord-01403faf49f2441c9fe1f5aa642fa0aa
출처 데이터셋
uspto-grants-1992_11
특허 번호
US05160661

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