Triethylamine → HCID 43810791, compound

To a solution of cyclopentylmethyl alcohol (51.1 g, 0.51 mol) and triethylamine (82.6 g, 0.82 mol) in tetrahydrofuran (510 mL) was added dropwise methanesulfonyl chloride (67.2 g, 0.59 mmol) over 55 minutes with keeping the temperature below 10° C., and the reaction mixture was stirred for 1 hour. To the mixture was added water (380 mL) with keeping the internal temperature below 10° C., and the mixture was extracted with toluene (765 mL). The organic layer was dried over anhydrous MgSO4, and the solvent was evaporated under reduced pressure to give a crude product of Compound (Ie) (86.9 g). The crude product of Compound (Ie) (50 g, equivalent to 0.28 mol) and hydrazine monohydrate (84.3 g, 1.7 mol) were dissolved in ethanol (281 mL), and the reaction mixture was stirred at 45° C. to 55° C. for 7 hours and then cooled to room temperature. To the resultant was added water (94 mL), and the mixture was extracted with chloroform (562 mL). The organic layer was washed with water (94 mL) twice, and dried over anhydrous Na2SO4. To the solution was added conc. HCl (85 g) at an internal temperature below 10° C., methanol (190 mL) was added thereto to dissolve the solid, and the solvent was evaporated under reduced pressure. To the concentrated residue was added 2-propanol (234 mL), and the solvent was evaporated under reduced pressure four times. To the concentrated residue was added 2-propanol (85 mL). The mixture was heated to 40° C., n-hexane (170 mL) was added dropwise thereto at 40° C. over 30 minutes, and the mixture was stirred at 40° C. for 1 hour. Then, the mixture was cooled to 10° C. over 1 hour and stirred at an internal temperature below 10° C. for 1 hour. The resulting precipitate was collected by filtration, washed with a mixed solution of cooled n-hexane/2-propanol (2:1) (36 mL), and dried under reduced pressure to give the title compound (33.6 g, 64%) as a white powder.

1. customthe temperature below 10° C.
2. customthe internal temperature below 10° C.
3. extractionthe mixture was extracted with toluene (765 mL)
4. dry with materialThe organic layer was dried over anhydrous MgSO4
5. customthe solvent was evaporated under reduced pressure
6. customto give a crude product of Compound (Ie) (86.9 g)
7. stirringthe reaction mixture was stirred at 45° C. to 55° C. for 7 hours
8. extractionthe mixture was extracted with chloroform (562 mL)
9. washThe organic layer was washed with water (94 mL) twice
10. dry with materialdried over anhydrous Na2SO4
11. additionTo the solution was added conc. HCl (85 g) at an internal temperature below 10° C., methanol (190 mL)
12. additionwas added
13. dissolutionto dissolve the solid
14. customthe solvent was evaporated under reduced pressure
15. additionTo the concentrated residue was added 2-propanol (234 mL)
16. customthe solvent was evaporated under reduced pressure four times
17. additionTo the concentrated residue was added 2-propanol (85 mL)
18. temperatureThe mixture was heated to 40° C.
19. additionn-hexane (170 mL) was added dropwise
20. waitat 40° C. over 30 minutes
21. stirringthe mixture was stirred at 40° C. for 1 hour
22. temperatureThen, the mixture was cooled to 10° C. over 1 hour
23. stirringstirred at an internal temperature below 10° C. for 1 hour
24. filtrationThe resulting precipitate was collected by filtration
25. washwashed with a mixed solution of cooled n-hexane/2-propanol (2:1) (36 mL)
26. customdried under reduced pressure

ORD record

ord-66c7218fe211433e8dbbd34028237afb

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809383B2