Hydrochloric Acid → HCID 58695801, compound

To a solution of (S) (−)-α,α-dephenyl-2-pyrrolidinemethanol (0.724 g, 2.86 mmol) in anhydrous tetrahydrofuran (25 mL) was added trimethylborate (0.446 g, 4.29 mmol) all at once and stirred at room temperature for 1 h. The borane dimethylsulfide complex (7.15 mL, 14.3 mmol, 2.0 M in THF) was added dropwise over a period of 1 h. The mixture was then cooled to 0° C. with an ice-bath and a solution of ethyl 3-(4-chloro-2-propionylphenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate (2-7) (5.00 g, 14.9 mmol) in 15 mL of anhydrous tetrahydrofuran was added dropwise over a period of 3 h (keeping the reaction temperature below 4° C.). The reaction mixture was allowed to warm slowly up to room temperature and stirred overnight. After the reaction was complete, the mixture was added portionwise to a stirring mixture of 2 N HCl (125 mL) and EtOAc (100 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated. Purification of the crude residue by flash chromatography over silica gel (5% ethyl acetone/dichloromethane as eluent) afforded (2-8) as a colorless oil.

1. temperatureThe mixture was then cooled to 0° C. with an ice-bath
2. customthe reaction temperature below 4° C.
3. temperatureto warm slowly up to room temperature
4. stirringstirred overnight
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over anhydrous MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification of the crude residue by flash chromatography over silica gel (5% ethyl acetone/dichloromethane as eluent)

ORD record

ord-b5e5d6da41114c42825bc162b3b7649b

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07276520B2