3-Bromothiophene → 1-Butyl-4-[hydroxy(di-3-thienyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide

HRID 2167552노트

반응식

HRID 2167552 반응식
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[Br:6][C:7]1[CH:11]=[CH:10][S:9][CH:8]=1.[N:12]12[CH2:19][CH2:18][C:15]([C:20]([O:22]CC)=O)([CH2:16][CH2:17]1)[CH2:14][CH2:13]2>C(OCC)C.C1COCC1.CCOCC.CS(C)=O>[Br-:6].[CH2:1]([N+:12]12[CH2:13][CH2:14][C:15]([C:20]([OH:22])([C:7]3[CH:11]=[CH:10][S:9][CH:8]=3)[C:7]3[CH:11]=[CH:10][S:9][CH:8]=3)([CH2:16][CH2:17]1)[CH2:18][CH2:19]2)[CH2:2][CH2:3][CH3:4]

참가 물질

7

반응물 3

HCID 133833-BromothiopheneHCID 573424Ethyl 1-azabicyclo(2.2.2)octane-4-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 689654491-Butyl-4-[hydroxy(di-3-thienyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide수율 9.4%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 3283Diethyl Ether용매HCID 21868444Ether tetrahydrofuran용매

실험 절차

A solution of n-Butyl lithium (2.5M in hexanes, 5.0 mL, 12.5 mmol) was chilled to −78° C. under Ar. 3-Bromothiophene (1.15 mL, 12.3 mmol) dissolved in ethyl ether (4.0 mL) was slowly added to the reaction mixture. The reaction was stirred for 30 min and then ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.7640 g, 4.16 mmol) in THF/Et2O (4 mL/4 mL) was added. The reaction was allowed to warm up from −78° C. to room temperature over 16 h then slowly quenched with water. The reaction was concentrated and the resulting brown solid was taken up in water and DCM. The organic phase was separated, dried over MgSO4, filtered and concentrated under vacuum to give a brown solid. The solid was dissolved in DMSO and purified by preparatory HPLC to give the title compound (0.1736 g, 9.4%). EI-MS m/z 362 (M+) Rt (1.73 min).

후처리

  1. additionwas slowly added to the reaction mixture
  2. temperatureto warm up from −78° C. to room temperature over 16 h
  3. customthen slowly quenched with water
  4. concentrationThe reaction was concentrated
  5. customThe organic phase was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customto give a brown solid
  10. custompurified by preparatory HPLC

출처 및 근거

ORD 기록
ord-dc58ca25fcb04d2fbd63b44d8a6fde7a
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045469B2

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