Methanol → 3-(Pyridin-2-yl)-1-azabicyclo[2.2.2]octan-3-ol

HRID 2226146Notes

Reaction equation

C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[N:13]12[CH2:20][CH2:19][CH:16]([CH2:17][CH2:18]1)[C:15](=[O:21])[CH2:14]2.CO>CCOCC>[OH:21][C:15]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:16]2[CH2:19][CH2:20][N:13]([CH2:18][CH2:17]2)[CH2:14]1

Participants

Conditions

Temperature: -70 °C

Procedure

n-Butyl lithium (1.6M in hexanes, 17.4 ml, 27.9 mmol) was added dropwise to a solution of 2-bromopyridine (2.66 ml, 27.9 mmol) in ether (75 ml) cooled to -70° C. After 30 min a solution of 3-quinuclidinone (3.49 g, 27.9 mmol) in ether (25 ml) was added and the reaction mixture allowed to warm to -20° C. over 1 h. Methanol (50 ml) was added and the solution concentrated. The crude product was chromatographed through silica-gel using dichloromethane/methanol/ammonia (89:10:1) as eluent to give 1.58 g of the title compound as a tan solid. The dihydrochloride salt was prepared; m.p. 210°-5° C.; Found C, 51.82; H, 6.50; N, 9.98. C12H18N2Cl2O requires C, 51.99; H, 6.55; N, 10.10; δ(360 MHz, D2O) 8.792 (1H, d, J=5.4 Hz, py-H), 8.528 (1H, dt, J=8.1, 1.5 Hz, py-H), 8.139 (1H, d, J=8.1 Hz, py-H), 7.961 (1H, t, J=6.7 Hz, py-H), 4.177 (1H, d, J=14.3 Hz, H-2ax), 3.661 (1H, d, J=14.3 Hz, H-2eq), 3.54-3.35 (4H, m, H2 -6 and H2 -7) 2.55-1.65 (5H, m, H-4, H2 -5 and H2 -8); m/e 204 (M+).

Workup

temperatureto warm to -20° C. over 1 h
concentrationthe solution concentrated
customThe crude product was chromatographed through silica-gel

Sources & evidence

ORD record: ord-25cd3d8b169e4efc99f11ccd9f2b41a7
Source dataset: uspto-grants-1994_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05346906

Reaction notes

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