Trifluoromethanesulfonic acid → 1-((4-Bromo-2-chloro-5-fluorobenzyl)oxy)adamantane

HRID 1427830노트

반응식

HRID 1427830 반응식
Cl[C:2](Cl)(Cl)[C:3](=N)[O:4][CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([Br:13])=[CH:8][C:7]=1[Cl:14].[C:18]12(O)[CH2:27]C3C[CH:24]([CH2:26][CH:20]([CH2:21]3)[CH2:19]1)[CH2:25]2.FC(F)(F)S(O)(=O)=O>C(Cl)Cl.C1CCCCC1>[Br:13][C:9]1[C:10]([F:12])=[CH:11][C:6]([CH2:5][O:4][C:3]23[CH2:27][CH:18]4[CH2:19][CH:20]([CH2:26][CH:24]([CH2:25]4)[CH2:2]2)[CH2:21]3)=[C:7]([Cl:14])[CH:8]=1

참가 물질

6

반응물 3

HCID 62406Trifluoromethanesulfonic acidHCID 641521-AdamantanolHCID 867028534-Bromo-2-chloro-5-fluorobenzyl 2,2,2-trichloroacetimidate

생성물 1

HCID 867028541-((4-Bromo-2-chloro-5-fluorobenzyl)oxy)adamantane수율 44%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8078Cyclohexane용매

실험 절차

To a solution of 4-bromo-2-chloro-5-fluorobenzyl 2,2,2-trichloroacetimidate (3.95 g, 16.49 mmol) and 1-adamantanol (0.65 g, 4.26 mmol) in methylene chloride (15 mL) and cyclohexane (30 mL) was added trifluoromethanesulfonic acid (0.04 mL, 0.45 mmol) at 0° C. The reaction mixture was stirred for 56 h at ambient temperature and quenched by addition of saturated sodium bicarbonate solution (10 mL), and then diluted with methylene chloride (100 mL). The organic layer was separated and washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) and recrystallization from methanol afforded 1-((4-bromo-2-chloro-5-fluorobenzyl)-oxy)adamantane as a colorless solid (0.70 g, 43%): 1H NMR (300 MHz, CDCl3) δ 7.47 (d, J=6.3 Hz, 1H), 7.37 (d, J=9.3 Hz, 1H), 4.48 (s, 2H), 2.16 (br s, 3H), 1.82-1.80 (m, 6H), 1.70-1.55 (m, 6H).

후처리

  1. customquenched by addition of saturated sodium bicarbonate solution (10 mL)
  2. additiondiluted with methylene chloride (100 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue
  8. customby column chromatography (5% ethyl acetate in hexanes) and recrystallization from methanol

출처 및 근거

ORD 기록
ord-f5908e551c114a48aee683d5c1e612ee
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933236B2

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