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

HRID 2294955Notes

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-quinuclidone (24 g) in dry tetrahydrofuran (100 ml) was then added to the mixture 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 room 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 (21.2g), m.p. 193°-197° C.; NMR (DMSO-d6): 1.25-1.3(1H, m), 1.4-1.6(1H, m), 1.7-1.95(3H, m), 2.55-2.8(5H, m), 2.95(1H, d), 3.2(1H, s) and 5.4(1H, s); m/Z 152 (M+H).

Workup

stirringthe mixture stirred for 1 hour at -70° C
temperatureto warm to room 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-35c4c14ebacf47d69f771a10d3f22df6
Source dataset: uspto-grants-1997_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05691349

Reaction notes

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