Diisopropylamine → 2-(3-Hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetic acid t-butyl ester
Reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH3:14].[N:21]12[CH2:28][CH2:27][CH:24]([CH2:25][CH2:26]1)[C:23](=[O:29])[CH2:22]2>O1CCCC1.O>[C:17]([O:16][C:13](=[O:15])[CH2:14][C:23]1([OH:29])[CH:24]2[CH2:27][CH2:28][N:21]([CH2:26][CH2:25]2)[CH2:22]1)([CH3:20])([CH3:19])[CH3:18]Participants
Conditions
- Temperature
- -78 °C
Procedure
To a solution of diisopropylamine (6.7 mL) in tetrahydrofuran (THF) (20 mL) at 0° C. was added n-butyllithium (2.3M in hexanes; 20 mL). The reaction mixture was stirred for 40 minutes and then cooled to -78° C. To this mixture a solution of t-butyl acetate (6.4 mL) in THF (10 mL) was added dropwise and stirring was continued for an additional 15 minutes. Quinuclidin-3-one (5 g) in THF (15 mL) was added to the mixture dropwise and the mixture was allowed to warm to 0° C. over 1 hour. To this solution water (100 mL) was added, the solution was extracted twice with chloroform and the combined extracts were washed once with brine. The resulting solution was dried over MgSO4, filtered, and evaporated in vacuo to give 9.53 g of the subtitle compound as an off-white solid.
Workup
- stirringstirring
- waitwas continued for an additional 15 minutes
- temperatureto warm to 0° C. over 1 hour
- extractionthe solution was extracted twice with chloroform
- washthe combined extracts were washed once with brine
- dry with materialThe resulting solution was dried over MgSO4
- filtrationfiltered
- customevaporated in vacuo
Sources & evidence
- ORD record
- ord-63212152804141309c9013c6146c7836
- Source dataset
- uspto-grants-2000_08
- Patent number
- US06110914
Reaction notes
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