Tetrahydrofuran → 3-(3,3-Diphenyl-1-butynyl)quinuclidin-3-ol

HRID 900778Notes

Reaction equation

HRID 900778 reaction equation
[CH3:1][C:2]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[C:3]#[CH:4].[Li]CCCC.CCCCCC.[N:28]12[CH2:35][CH2:34][CH:31]([CH2:32][CH2:33]1)[CH2:30][C:29]2=O.C1C[O:40]CC1>CCOCC>[C:11]1([C:2]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)([CH3:1])[C:3]#[C:4][C:30]2([OH:40])[CH:31]3[CH2:34][CH2:35][N:28]([CH2:33][CH2:32]3)[CH2:29]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 8058HexaneHCID 5661191-azabicyclo[2.2.2]octan-2-oneHCID 10929756(1-Methyl-1-phenyl-2-propynyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 99242603-(3,3-Diphenyl-1-butynyl)quinuclidin-3-olYield 61%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

(1-methyl-1-phenyl-2-propynyl)benzene (Dehmlow E., Tetrahedron Lett. (1971), 563-566) (380 mg, 1.84 mmol.) in THF (10 ml) at −78° C. was treated with a 1.6 N solution of BuLi in hexane (1.21 ml, 1.94 mmol). After 30 minutes, at the same temperature, a solution of quinuclidinone (300 mg, 2.4 mmol) in THF (5 ml) was added dropwise. After 1 hour, the reaction was left at room temperature for 12 hours. The mixture was then diluted with ether and washed with water (twice) and brine. The organic phase was dried over MgSO4 and evaporated to dryness. Chromatography on silica gel (elution: CH2Cl2/EtOH/NH4OH 90/10/0.1) gave 3-(3,3-diphenyl-1-butynyl)quinuclidin-3-ol 195 as a white solid (380 mg, 61%). This compound was used as such in the next step.

Workup

  1. waitAfter 1 hour
  2. waitthe reaction was left at room temperature for 12 hours
  3. washwashed with water (twice) and brine
  4. dry with materialThe organic phase was dried over MgSO4
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-62c944c1be1d4d4bb9cb042cbaa33ff7
Source dataset
uspto-grants-2008_04
Patent number
US07361668B2

Reaction notes

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