8-Methyl-8-azabicyclo(3.2.1)octan-3-ol → 8-Azabicyclo(3.2.1)octan-3-ol, 8-methyl-, 3-methanesulfonate
Reaction equation
[CH3:1][N:2]1[CH:6]2[CH2:7][CH:8]([OH:10])[CH2:9][CH:3]1[CH2:4][CH2:5]2.C(N(CC)CC)C.[CH3:18][S:19](Cl)(=[O:21])=[O:20]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:1][N:2]1[CH:6]2[CH2:5][CH2:4][CH:3]1[CH2:9][CH:8]([O:10][S:19]([CH3:18])(=[O:21])=[O:20])[CH2:7]2Participants
Procedure
A solution of tropine (10.0 g, 70.8 mmol), 4-dimethylaminopyridine (80 mg, 0.60 mmol), and triethylamine (11.0 mL, 78.9 mmol) in DCM (125 mL) was cooled to 0° C., charged with methanesulfonyl chloride (5.50 mL, 71.0 mmol), slowly allowed to warm to rt, and stirred for an additional 16 h at rt. The reaction mixture was partitioned between CHCl3 and sat. NaHCO3, and the layers were separated. The aqueous layer was extracted with CHCl3 (3×) and the combined organic fractions were washed with sat. NaHCO3 (2×), brine (2×), dried over Na2SO4, filtered, and concentrated in vacuo resulting in the title compound as a pale brown solid. This material was taken on to the next step without further purification. 1H NMR (400 MHz, CDCl3): δ=1.94-2.09 (m, 6H), 2.20 (dt, J=15.4, 4.2 Hz, 2H), 2.28 (s, 3H), 2.99 (s, 3H), 3.10-3.17 (m, 2H), 4.94 (t, J=5.1 Hz, 1H).
Workup
- customThe reaction mixture was partitioned between CHCl3 and sat. NaHCO3
- customthe layers were separated
- extractionThe aqueous layer was extracted with CHCl3 (3×)
- washthe combined organic fractions were washed with sat. NaHCO3 (2×), brine (2×)
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-5e1778ab88964de1a17eae8865f9b145
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08178668B2
Reaction notes
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