Hexane → 3-[3-Hydroxy-3-(4-methoxyphenyl)-3-(2-thienyl)-1-propynyl]quinuclidin-3-ol

HRID 900775Notes

Reaction equation

HRID 900775 reaction equation
[Li]CCCC.CCCCCC.[C:12]([C:14]1([OH:22])[CH:19]2[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]2)[CH2:15]1)#[CH:13].[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:33]2[S:34][CH:35]=[CH:36][CH:37]=2)=[O:32])=[CH:27][CH:26]=1>C1COCC1>[OH:32][C:31]([C:28]1[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=1)([C:33]1[S:34][CH:35]=[CH:36][CH:37]=1)[C:13]#[C:12][C:14]1([OH:22])[CH:19]2[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]2)[CH2:15]1

Participants

6

Reactant 4

HCID 8058HexaneHCID 77812p-Anisyl thiophen-2-yl ketoneHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 178418339Butyllithium

Product 1

HCID 692922983-[3-Hydroxy-3-(4-methoxyphenyl)-3-(2-thienyl)-1-propynyl]quinuclidin-3-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1.6 N solution of BuLi in hexane (1.12 ml, 1.79 mmol) was added dropwise to a solution of 3-ethynyl-1-azabicyclo[2.2.2]octan-3-ol 47 (123 mg, 0.81 mmol) in THF (5 ml) at room temperature. After stirring for 30 minutes, (4-methoxyphenyl)(2-thienyl)methanone (231 mg, 1.06 mmol, commercial) in THF (1 ml) was added slowly. After 2 hours, the reaction was quenched by addition of saturated aqueous NH4Cl solution and diluted with AcOEt. The organic phase was washed with brine, dried over Na2SO4 and evaporated. The yellowish oil was purified by chromatography on silica gel (CH2Cl2/MeOH 85/15) and 3-[3-hydroxy-3-(4-methoxyphenyl)-3-(2-thienyl)-1-propynyl]quinuclidin-3-ol 152 was obtained as a white solid (41 mg, 14%, mixture of diastereomers).

Workup

  1. waitAfter 2 hours
  2. customthe reaction was quenched by addition of saturated aqueous NH4Cl solution
  3. additiondiluted with AcOEt
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe yellowish oil was purified by chromatography on silica gel (CH2Cl2/MeOH 85/15)

Sources & evidence

ORD record
ord-34f0e29cbfac46a5b353d9f10fb802e7
Source dataset
uspto-grants-2008_04
Patent number
US07361668B2

Reaction notes

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