Pyridine → Methanesulfonic acid 2-(6-benzenesulfonyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-ethyl ester

Temperature

0 °C

A solution of (6-benzenesulfonyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-acetic acid methyl ester (5.22 g, 14.56 mmol) in anhydrous Et2O (50 mL) was cooled to 0° C. under argon, and 21.84 mL of lithium aluminum hydride (21.84 mmol) in THF was added dropwise via syringe. An additional 50 mL of dry THF was added, and the reaction mixture was stirred for 1 hour. The reaction mixture was carefully quenched by addition of 500 mL water, and the resulting aqueous mixture was extracted twice with 250 mL of EtOAc. Evaporation of the organic layer yielded a crude oil which was purified by elution through silica gel with 1:1 hexanes:EtOAc. The solvent was evaporated to give a solid that was dissolved in 50 mL dry methylene chloride. The solution was cooled to 0° C., and pyridine (4.0 mL, 49.5 mmol) and methanesulfonyl chloride (1.69 mL, 21.84 mmol) were added. The reaction mixture was stirred for 3 hours, during which time the reaction mixture was allowed to warm to room temperature. The reaction mixture was poured into 500 mL of saturated aqueous NaHCO3, and the mixture was extracted three times with 250 mL of EtOAc. The combined organic layers were washed with water, brine, and dried on MgSO4. The solvent was removed under reduced pressure to give an oil that was dissolved in benzene and azeotroped to remove residual pyridine. Solvent was removed, and the resulting oil was dissolved in methylene chloride and eluted through silica gel with 1:1 hexanes:EtOAc. Solvent was again removed, to afford methanesulfonic acid 2-(6-benzenesulfonyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-ethyl ester as a white solid (4.44 g, 11.25 mmol, 77.3%) MS: 396 (M+H)+.

1. customThe reaction mixture was carefully quenched by addition of 500 mL water
2. extractionthe resulting aqueous mixture was extracted twice with 250 mL of EtOAc
3. customEvaporation of the organic layer
4. customyielded a crude oil which
5. customwas purified by elution through silica gel with 1:1 hexanes
6. customThe solvent was evaporated
7. customto give a solid
8. stirringThe reaction mixture was stirred for 3 hours, during which time the reaction mixture
9. temperatureto warm to room temperature
10. extractionthe mixture was extracted three times with 250 mL of EtOAc
11. washThe combined organic layers were washed with water, brine
12. customdried on MgSO4
13. customThe solvent was removed under reduced pressure
14. customto give an oil that
15. customazeotroped
16. customto remove residual pyridine
17. customSolvent was removed
18. dissolutionthe resulting oil was dissolved in methylene chloride
19. washeluted through silica gel with 1:1 hexanes
20. customSolvent was again removed

ORD record

ord-aa2908e13da84568b969260ffd812c54

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07981923B2