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

HRID 1782453ノート

反応式

HRID 1782453 の反応式
[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]

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 3283Diethyl Ether溶媒HCID 21868444Ether tetrahydrofuran溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-3dcb0f0e983d476ab3b35211f538f30f
出典データセット
uspto-grants-2009_03
特許番号
US07498440B2

反応ノート

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