Acetic Acid → HCID 19825704, compound

Temperature

-65 °C

A stirred solution of lithium diisopropylamide (4.0 ml of 1 5M cyclohexane solution; 0.0060 mole) in dry tetrahydrofuran (100 ml ) at -65° C. under nitrogen was treated with a solution of 2-[2-(4-methylphenylsulphonyl)ethyl ]-1,3-dioxolane (compound D5 in EP-0322182, 1.54 g, 0.0060 mole) in dry tetrahydrofuran (5 ml). After stirring the resulting solution at -65° C. for 10 minutes, a solution of crude 1-azabicyclo[3.1.1]hept-5-ylcarboxaldehyde (D6, 550 mg, 0.0044 mole) in dry THF (8 ml ) was added. The reaction mixture was allowed to warm up to -20° C. over 30 minutes, then treated with glacial acetic acid (5 ml ) and concentrated in vacuo. The residue was dissolved in glacial acetic acid (100 ml ), treated with 4-toluenesulphonic acid (20 mg) and heated under reflux for 24 h. The solution was concentrated in vacuo and the residue basified with concentrated potassium carbonate solution and extracted with chloroform (2×80 ml ). The combined extracts were dried (Na2SO4) and concentrated in vacuo to leave a brown oil, which was distilled in a Kugelrohr apparatus. The material boiling at 130°-150° C. at 0.1 mmHg was collected and then chromatographed on basic alumina eluting initially with ether to remove impurities, then with 10% methanol/ethyl acetate to remove the title compound (E12), which was obtained as a colourless oil (4 mg).

1. temperatureto warm up to -20° C. over 30 minutes
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in glacial acetic acid (100 ml )
4. additiontreated with 4-toluenesulphonic acid (20 mg)
5. temperatureheated
6. temperatureunder reflux for 24 h
7. concentrationThe solution was concentrated in vacuo
8. extractionthe residue basified with concentrated potassium carbonate solution and extracted with chloroform (2×80 ml )
9. dry with materialThe combined extracts were dried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customto leave a brown oil, which
12. distillationwas distilled in a Kugelrohr apparatus
13. customThe material boiling at 130°-150° C. at 0.1 mmHg was collected
14. customchromatographed on basic alumina eluting initially with ether
15. customto remove impurities
16. customwith 10% methanol/ethyl acetate to remove the title compound (E12)

ORD record

ord-462a58d8a85548fa83d2149ee4263789

Source dataset

uspto-grants-1991_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05043343