3,4-dihydro-2H-pyran → 5-bromo-4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole

HRID 475228노트

반응식

HRID 475228 반응식
[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[NH:6][CH:7]=[N:8][C:4]=2[C:3]=1[F:11].[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1COCC1>[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[N:6]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][O:12]3)[CH:7]=[N:8][C:4]=2[C:3]=1[F:11]

참가 물질

5

반응물 3

HCID 80803,4-dihydro-2H-pyranHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 594744775-bromo-4-fluoro-1H-1,3-benzodiazole

생성물 1

HCID 866947315-bromo-4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole수율 78.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 144 (24 g, 0.111 mol) in dry THF (720 mL) was added 3,4-dihydro-2H-pyran (28.1 g, 0.334 mol) and camphorsulfonic acid (2.6 g, 0.011 mol) then heated to reflux for 16 h. The resulting mixture was concentrated and the residue purified by SiO2 chromatography eluting with 20% EtOAc/petroleum ether to afford 26 g (78%) of 5-bromo-4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole (146) as pale yellow oil: 1H-NMR (400 MHz, RT, DMSO-d6): δ 1.57-1.63 (m, 2H), 1.70-1.74 (m, 1H), 1.91-2.04 (m, 2H), 2.15-2.19 (m, 1H), 3.73-3.77 (m, 1H), 3.96-4.03 (m, 1H), 5.68-5.71 (dd, 1H), 7.50-7.53 (d, 2H), and 8.51 (s, 1H); MS (ESI): m/z=301.0 [M+1]+.

후처리

  1. temperaturethen heated
  2. temperatureto reflux for 16 h
  3. concentrationThe resulting mixture was concentrated
  4. customthe residue purified by SiO2 chromatography
  5. washeluting with 20% EtOAc/petroleum ether

출처 및 근거

ORD 기록
ord-43415d75bb2a4056a0712e3cc8c77ed2
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637537B2

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