(+-)-3-Quinuclidinol → Racemic 6-amino-4-(quinuclidin-3-yloxy)nicotinonitrile

A solution of KHMDS in THF (1 M, 6.6 ml, 6.60 mmol) was added drop wise to a solution of racemic quinuclidin-3-ol (928 mg, 7.29 mmol) in THF (2 ml) at room temperature. After 55 min a solution of 6-amino-4-fluoronicotinonitrile (intermediate 21, 500 mg, 3.65 mmol) in THF (2 ml) was added and the reaction mixture stirred for 3 days at room temperature. The reaction mixture was partitioned between saturated aqueous NH4Cl and DCM, extracted with DCM (8×), the combined DCM layers were dried over Na2SO4 and evaporated. The residue was preabsorbed onto silica gel and purified by normal phase chromatography with a 12 g RediSep® silica column, eluting with a gradient from DCM to 20% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as a beige solid. (UPLC-MS 6) tR 0.32; ESI-MS 245.2 [M+H]+.

1. customThe reaction mixture was partitioned between saturated aqueous NH4Cl and DCM
2. extractionextracted with DCM (8×)
3. dry with materialthe combined DCM layers were dried over Na2SO4
4. customevaporated
5. customThe residue was preabsorbed onto silica gel
6. custompurified by normal phase chromatography with a 12 g RediSep® silica column
7. washeluting with a gradient from DCM to 20% MeOH in DCM
8. additionProduct containing fractions
9. customevaporated

ORD record

ord-e6ece83d85674a7784aaef12ea1a3f0a

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266883B2