Dichloromethane → HCID 18594294, compound

To a solution containing 3.07 ml. of methylene chloride in 60 ml. of anhydrous tetrahydrofuran cooled to -70°, there was added over a period of 1 hour 44 mmoles of n-butyllithium in 28 ml. of hexane under an atmosphere of dry nitrogen. Stirring of the mixture at the same temperature was continued for 20 minutes and then followed by the dropwise addition of 5.19 g. (20 mmoles) of 2-[1-benzoyl-3(R)-vinyl-4(S)-piperidinyl]acetaldehyde in 30 ml. of anhydrous tetrahydrofuran. After 30 minutes, the reaction was quenched by the addition of 30 ml. of water. The mixture was allowed to warm up to room temperature and was subsequently extracted three times with ether. The combined ether extracts were washed with water, dried over sodium sulfate and evaporated to dryness. The residue was dissolved in 80 ml. of 3N hydrochloric acid. The acidic solution was washed with ether and neutralized with 3N sodium hydroxide. The solution was washed again with ether, rendered alkaline by the addition of 3N sodium hydroxide and extracted with ether. The ether extract was washed with water, dried over sodium sulfate and evaporated to dryness. The residue (3.8 g.) was dissolved in ethanol and treated with an excess of ethanolic hydrogen chloride. The solvent was evaporated under reduced pressure and the resulting solid residue was crystallized from ethanol to give 2.0 g. of a mixture of epimeric 1,1-dichloro-3-[3(R)-vinyl-4(S)-piperidinyl]propan-2ε-ol hydrochlorides. Fractional crystallization from ethanol followed by recrystallization of the combined fractions from ethanol gave 1,1-dichloro-3-[3(R)-vinyl-4(S)-piperidinyl]propan-2(S)-ol hydrochloride, m.p. 225°-225.5°, [α]D25 -13.3° (c 1.02, methanol).

1. additionTo a solution containing 3.07 ml
2. additionfollowed by the dropwise addition of 5.19 g
3. waitAfter 30 minutes
4. customthe reaction was quenched by the addition of 30 ml
5. extractionwas subsequently extracted three times with ether
6. washThe combined ether extracts were washed with water
7. dry with materialdried over sodium sulfate
8. customevaporated to dryness
9. dissolutionThe residue was dissolved in 80 ml
10. washThe acidic solution was washed with ether and neutralized with 3N sodium hydroxide
11. washThe solution was washed again with ether
12. additionby the addition of 3N sodium hydroxide
13. extractionextracted with ether
14. extractionThe ether extract
15. washwas washed with water
16. dry with materialdried over sodium sulfate
17. customevaporated to dryness
18. dissolutionThe residue (3.8 g.) was dissolved in ethanol
19. additiontreated with an excess of ethanolic hydrogen chloride
20. customThe solvent was evaporated under reduced pressure
21. customthe resulting solid residue was crystallized from ethanol
22. customto give 2.0 g
23. customFractional crystallization from ethanol
24. customfollowed by recrystallization of the combined fractions from ethanol

ORD record

ord-db3d58a21dde46f996c3d48505304933

Source dataset

uspto-grants-1976_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US03931192