Hydrochloric Acid → HCID 178520920, Verbindung

Temperatur

0 °C

To a stirred solution of methyl trans-4-(4-chlorophenyl)cyclohexanecarboxylate (compound of formula (VIIa)) (50.5 g, 200 mmol) in tetrahydrofuran (400 mL) at 0° C. under argon was added a 1M solution of lithium aluminium hydride in tetrahydrofuran (100 mL, 100 mmol) and the reaction mixture stirred for 30 minutes. The reaction mixture was cooled to 0° C. and 1M aqueous hydrochloric acid (500 mL, 500 mmol) was added and the mixture stirred for 5 minutes. The aqueous was separated and extracted with ethyl acetate (250 mL) then the combined organics were washed twice with water (2×125 mL). The resulting organics were concentrated under vacuum to a volume of 150 mL. The residue was diluted with ethyl acetate (250 mL) and the mixture concentrated under vacuum to a volume of 150 mL. The residue was diluted with ethyl acetate (250 mL) and the mixture concentrated under vacuum to a volume of 150 mL. The residue was diluted with ethyl acetate (250 mL) and the mixture concentrated under vacuum to a volume of 150 mL. To the resulting stirred mixture, at ambient temperature under argon, was added dimethyl sulfoxide (100 mL) and triethylamine (112 mL, 804 mmol). The mixture was cooled to 0° C. then pyridine sulphur trioxide complex (64 g, 402 mmol) was added in 4 equal portions and the reaction mixture stirred between 0 and 20° C. for 2 hours. Ethyl acetate (400 mL) was added, the mixture cooled to 0° C. with stirring and then 1M aqueous hydrochloric acid (400 mL, 400 mmol) was added. The resulting mixture was stirred at ambient temperature for 5 minutes then the organic layer was separated, diluted by the addition of ethyl acetate (500 mL) and washed with water (250 mL). The resulting organics were concentrated under vacuum to a volume of 200 mL, the residue diluted by the addition of ethyl acetate (500 mL) and then concentrated to a volume of 200 mL. The resulting mixture containing the title compound was used in the next step without analysis or purification.

1. stirringthe mixture stirred for 5 minutes
2. customThe aqueous was separated
3. extractionextracted with ethyl acetate (250 mL)
4. washthe combined organics were washed twice with water (2×125 mL)
5. concentrationThe resulting organics were concentrated under vacuum to a volume of 150 mL
6. additionThe residue was diluted with ethyl acetate (250 mL)
7. concentrationthe mixture concentrated under vacuum to a volume of 150 mL
8. additionThe residue was diluted with ethyl acetate (250 mL)
9. concentrationthe mixture concentrated under vacuum to a volume of 150 mL
10. additionThe residue was diluted with ethyl acetate (250 mL)
11. concentrationthe mixture concentrated under vacuum to a volume of 150 mL
12. stirringTo the resulting stirred mixture
13. temperatureThe mixture was cooled to 0° C.
14. additionpyridine sulphur trioxide complex (64 g, 402 mmol) was added in 4 equal portions
15. stirringthe reaction mixture stirred between 0 and 20° C. for 2 hours
16. temperaturethe mixture cooled to 0° C.
17. stirringwith stirring
18. stirringThe resulting mixture was stirred at ambient temperature for 5 minutes
19. customthe organic layer was separated
20. additiondiluted by the addition of ethyl acetate (500 mL)
21. washwashed with water (250 mL)
22. concentrationThe resulting organics were concentrated under vacuum to a volume of 200 mL
23. additionthe residue diluted by the addition of ethyl acetate (500 mL)
24. concentrationconcentrated to a volume of 200 mL
25. additionThe resulting mixture containing the title compound
26. customwas used in the next step without analysis or purification

ORD-Eintrag

ord-459991b810d8487caf6eb38fe01a57ea

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08598387B2