Hydrochloric Acid → 917805-74-4

Hydrochloric acid (0.02 N; 15 mL) was added to a solution of tert-butyl (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate (Example 3; 15 g) in acetonitrile (150 mL) at 25° C. to 30° C. and stirred at the same temperature for 2 hours. After completion of the reaction, aqueous solution of sodium hydroxide (1.55 g in 30 mL) was added to the reaction mixture at 25° C. to 30° C. and stirred for 2.0 hours at 30° C. to 35° C. Acetonitrile was recovered completely under vacuum at 40° C. to 45° C. De-ionized water (30 mL) was added to the resulting residue at room temperature. Methyl tert-butyl ether (30 mL) was added to the mixture and stirred for 10 minutes. Layers were separated; methyl tert-butyl ether (30 mL) was added to the aqueous layer and stirred for 10 minutes. Layers were separated; the aqueous layer was cooled to 0° C. to 5° C. and added acetonitrile (75 ml) and sodium chloride (25 g) adjusted pH of 3.5 to 4.0 using hydrochloric acid (2N) at 0° C. to 5° C. Organic layer was separated and cooled to 0° C. to 5° C. To this pre-cooled organic layer, tert-butyl amine (1.9 g) was slowly added in 20 minutes at 0° C. to 5° C. and stirred for 1 hour at room temperature. The resulting mixture was cooled to 5° C. to 10° C., filtered, washed with acetonitrile (30 mL) and dried under vacuum at 40° C. to 45° C. for 4 hours.

1. additionwas added to the reaction mixture at 25° C. to 30° C.
2. stirringstirred for 2.0 hours at 30° C. to 35° C
3. customAcetonitrile was recovered completely under vacuum at 40° C. to 45° C
4. additionDe-ionized water (30 mL) was added to the resulting residue at room temperature
5. additionMethyl tert-butyl ether (30 mL) was added to the mixture
6. stirringstirred for 10 minutes
7. customLayers were separated
8. additionmethyl tert-butyl ether (30 mL) was added to the aqueous layer
9. stirringstirred for 10 minutes
10. customLayers were separated
11. temperaturethe aqueous layer was cooled to 0° C. to 5° C.
12. additionadded acetonitrile (75 ml) and sodium chloride (25 g)
13. customat 0° C. to 5° C
14. customOrganic layer was separated
15. temperaturecooled to 0° C. to 5° C
16. additionTo this pre-cooled organic layer, tert-butyl amine (1.9 g) was slowly added in 20 minutes at 0° C. to 5° C.
17. stirringstirred for 1 hour at room temperature
18. temperatureThe resulting mixture was cooled to 5° C. to 10° C.
19. filtrationfiltered
20. washwashed with acetonitrile (30 mL)
21. customdried under vacuum at 40° C. to 45° C. for 4 hours

ORD record

ord-18a459cef28843618551aa03d57c6705

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536330B2