Methanol → 3-Ethynyl-1-azabicyclo[2.2.2]octan-3-ol

HRID 861424Notes

Reaction equation

[CH2:1]([Li])[CH2:2]CC.C([Si](C)(C)C)#C.[N:12]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[C:14](=[O:20])[CH2:13]2.CO>CCCCC.O1CCCC1>[C:1]([C:14]1([OH:20])[CH:15]2[CH2:18][CH2:19][N:12]([CH2:17][CH2:16]2)[CH2:13]1)#[CH:2]

Participants

Conditions

Temperature: -70 °C

Procedure

A solution of n-butyl lithium (100 ml of a 2M solution in pentane) was added portion-wise over a period of 20 minutes to a stirred solution of ethynyltrimethylsilane (19.6 g) in dry tetrahydrofuran (400 ml) at -70° C. The mixture was stirred for 1 hour at -70° C. A solution of 3-quinuclidinone (2.4 g) in dry tetrahydrofuran (100 ml) was then added and the mixture stirred for 1 hour at -70° C. Methanol (1 ml) was then added to the mixture and the mixture allowed to warm to ambient temperature. The solvents were removed by evaporation. Methanol (500 ml) and potassium carbonate (40 g) were added to the residue and the mixture was stirred for 1 hour. The solvent was removed by evaporation. The residue was triturated with water (500 ml) and then dried in vacuo to give 3-ethynyl-3-hydroxy-quinuclidine as a solid, m.p. 193°-197° C.; NMR(DMSO-d6): 1.5-1.3(1H,m), 1.4-1.6(1H,m), 1.7-1.95(3H,m), 2.55-2.8(5H,m), 2.95(1H,d), 3.3(1H,d) and 5.4(1H,s); m/z 152 (M+H).

Workup

stirringthe mixture stirred for 1 hour at -70° C
temperatureto warm to ambient temperature
customThe solvents were removed by evaporation
additionMethanol (500 ml) and potassium carbonate (40 g) were added to the residue
stirringthe mixture was stirred for 1 hour
customThe solvent was removed by evaporation
customThe residue was triturated with water (500 ml)
customdried in vacuo

Sources & evidence

ORD record: ord-afa69d2b574b4909a405ecd47a8206cc
Source dataset: uspto-grants-1998_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05714496

Reaction notes

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