Potassium Carbonate → {4-[(S)-3-((S)-2-Methyl-pyrrolidin-1-yl)-cyclopentyl]-phenyl}-carbamic acid benzyl ester

Methanesulfonic acid (S)-3-(4-benzyloxycarbonylamino-phenyl)cyclopentyl ester (Intermediate 12) (510 mg, 1.31 mmol, 1 equiv.) was dissolved in 8 mL of anhydrous acetonitrile. This solution was transferred into a flask containing (S)-2-methyl-pyrrolidine (445 mg, 5.24 mmol, 4 equiv.) and K2CO3 (800 mg, 5.76 mmol, 4.4 equiv.). The suspension was de-gassed by vacuum/nitrogen exchange 3 times, and then, heated on an oil bath set at 80° C. under nitrogen with stirring for 16 h. TLC (5% MeOH in DCM for SM) showed the reaction was complete. Acetonitrile was removed in vacuo. The residue was taken in water (5 mL) and DCM (20 mL). The two layers were separated and the aqueous layer was extracted with DCM (2×10 mL). The combined extracts were washed with NaHCO3 aq. (5 mL), brine (5 mL), and dried (K2CO3). The solution was filtered. The filtrate was concentrated in vacuo to obtain a crude product which was purified on a silica gel column eluting with 5% 7N ammonia methanolic solution in DCM to afford 410 mg (84%) of the title compound.

1. customThis solution was transferred into a flask
2. customThe suspension was de-gassed by vacuum/nitrogen exchange 3 times
3. temperatureheated on an oil bath
4. customset at 80° C. under nitrogen
5. customAcetonitrile was removed in vacuo
6. customThe two layers were separated
7. extractionthe aqueous layer was extracted with DCM (2×10 mL)
8. washThe combined extracts were washed with NaHCO3 aq. (5 mL), brine (5 mL)
9. dry with materialdried (K2CO3)
10. filtrationThe solution was filtered
11. concentrationThe filtrate was concentrated in vacuo
12. customto obtain a crude product which
13. customwas purified on a silica gel column
14. washeluting with 5% 7N ammonia methanolic solution in DCM

ORD record

ord-f239e6d9e812471db12c1023a32676dd

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735385B2