Methanol → t-Butyl [5-chloro-2-(2-oxopyrrolidin-1-yl)benzyl]carbamate

(Step 2) To a solution (227 ml) of 5-chloro-2-(2-oxopyrrolidin-1-yl)benzonitrile obtained in Step 1 (5.0 g) and nickel chloride 6 hydrate (0.54 g) in methanol was gradually added sodium tetrahydroborate (4.29 g) at 0° C., and the mixture was stirred for 10 min. Water (50 ml) was slowly added to quench the reaction. The solvent was evaporated under reduced pressure. The residue was extracted with ethyl acetate and water, and the aqueous layer was extracted with ethyl acetate three times. The organic layers were combined, washed with saturated brine, dried over sodium sulfate, and filtered. The solvent was evaporated under reduced pressure. The residue was dissolved in methylene chloride (150 ml), a solution of di-t-butyl dicarbonate (5.15 ml) in methylene chloride (40 ml) was added to this solution, and triethylamine (7.82 ml) was added at room temperature. The reaction mixture was stirred at room temperature for 2 hr, and quenched with 5% hydrochloric acid (10 ml) and water (50 ml). The organic layer was washed with water and saturated brine, dried over sodium sulfate, and filtered. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:10→1:5) to give t-butyl [5-chloro-2-(2-oxopyrrolidin-1-yl)benzyl]carbamate (2.70 g).

1. customat 0° C.
2. customto quench
3. customthe reaction
4. customThe solvent was evaporated under reduced pressure
5. extractionThe residue was extracted with ethyl acetate and water
6. extractionthe aqueous layer was extracted with ethyl acetate three times
7. washwashed with saturated brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. customThe solvent was evaporated under reduced pressure
11. dissolutionThe residue was dissolved in methylene chloride (150 ml)
12. additiona solution of di-t-butyl dicarbonate (5.15 ml) in methylene chloride (40 ml) was added to this solution, and triethylamine (7.82 ml)
13. additionwas added at room temperature
14. stirringThe reaction mixture was stirred at room temperature for 2 hr
15. customquenched with 5% hydrochloric acid (10 ml) and water (50 ml)
16. washThe organic layer was washed with water and saturated brine
17. dry with materialdried over sodium sulfate
18. filtrationfiltered
19. customThe solvent was evaporated under reduced pressure
20. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:10→1:5)

ORD record

ord-efa642cc46a14628b7ae16e3f6d46047

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07982044B2