Chloroform → 5-chloro-N-[trans-3-(4-methanesulfonyl-phenyl)-2,2-dimethyl-cyclopropyl]-2-methoxy-benzamide

Chlorosulfonic acid (0.17 mL) was added at 0° C. to a solution of 5-chloro-N-(Trans-2,2-dimethyl-3-phenyl-cyclopropyl)-2-methoxy-benzamide (165 mg, 0.5 mmol) in chloroform (8 mL), and the resulting mixture was stirred at room temperature for 1.5 hour. The reaction was then quenched by addition of ice and the resulting mixture was extracted with diethyl ether. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL) and cooled to 0° C. Hydrazine (0.05 mL) was added and the resulting mixture was stirred for 18 hours. The reaction mixture was evaporated under reduced pressure and the residue was dissolved in ethanol (15 mL). Sodium acetate (205 mg) and methyl iodide (355 mg) were added and the resulting mixture was heated to reflux for 18 hours. The reaction mixture was then evaporated under reduced pressure and the residue was partitioned between brine and diethyl ether. The combined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was absorbed onto silica gel and purified by flash chromatography (EtOAc/hexane, 0-25%) to give 37 mg of 5-chloro-N-[trans-3-(4-methanesulfonyl-phenyl)-2,2-dimethyl-cyclopropyl]-2-methoxy-benzamide colorless viscous oil.

1. customThe reaction was then quenched by addition of ice
2. extractionthe resulting mixture was extracted with diethyl ether
3. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
4. filtrationfiltered
5. customevaporated under reduced pressure
6. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
7. temperaturecooled to 0° C
8. additionHydrazine (0.05 mL) was added
9. stirringthe resulting mixture was stirred for 18 hours
10. customThe reaction mixture was evaporated under reduced pressure
11. dissolutionthe residue was dissolved in ethanol (15 mL)
12. additionSodium acetate (205 mg) and methyl iodide (355 mg) were added
13. temperaturethe resulting mixture was heated
14. temperatureto reflux for 18 hours
15. customThe reaction mixture was then evaporated under reduced pressure
16. customthe residue was partitioned between brine and diethyl ether
17. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
18. filtrationfiltered
19. customevaporated under reduced pressure
20. customThe residue was absorbed onto silica gel
21. custompurified by flash chromatography (EtOAc/hexane, 0-25%)

ORD record

ord-391053a3834a41c79dc99274f4a1e64e

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723391B2