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

HRID 533809Notes

Reaction equation

HRID 533809 reaction equation
[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]

Participants

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolventHCID 21868444Ether tetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-d04e07a3a56f4fd3a224f349e3b9ca36
Source dataset
uspto-grants-2014_10
Patent number
US08853404B2

Reaction notes

Loading…