2-((R)-3-hydroxy-1,1-dimethyl-3-trifluoromethyl-6-trimethylsilanylhex-5-ynyl)benzamide → 2-((S)-3-hydroxy-1,1-dimethyl-3-trifluoromethylhex-5-ynyl)benzamide

To a stirred, ice-cooled, THF solution (100 mL) of 2-((R)-3-hydroxy-1,1-dimethyl-3-trifluoromethyl-6-trimethylsilanylhex-5-ynyl)benzamide (17.8 g, 46.2 mmol) n-tetrabutylammonium fluoride was added (51 mL of 1 M solution in THF, 51 mmol) dropwise via addition funnel. After 30 minutes, the reaction was quenched with 200 mL of 1 M HCl and further diluted with brine. The mixture was extracted with ethyl acetate. The combined extract was washed with water and brine, dried over anhydrous sodium sulfate, and the solvent removed in vacuo. The residue was redissolved in dichloromethane and the solvent evaporated. The residue was then dissolved in 30 mL of diethyl ether and triturated with hexanes. The precipitated solid was filtered. The filtrate was collected and the solvent evaporated, and the residue treated with diethyl ether/hexanes as before to obtain more solid precipitate. The solids were combined and dried in vacuo to give 2-((S)-3-hydroxy-1,1-dimethyl-3-trifluoromethylhex-5-ynyl)benzamide (10 g, 33% over two steps). This material was used without further purification.

1. temperatureTo a stirred, ice-cooled
2. additiondropwise via addition funnel
3. customthe reaction was quenched with 200 mL of 1 M HCl
4. additionfurther diluted with brine
5. extractionThe mixture was extracted with ethyl acetate
6. extractionThe combined extract
7. washwas washed with water and brine
8. dry with materialdried over anhydrous sodium sulfate
9. customthe solvent removed in vacuo
10. dissolutionThe residue was redissolved in dichloromethane
11. customthe solvent evaporated
12. dissolutionThe residue was then dissolved in 30 mL of diethyl ether
13. customtriturated with hexanes
14. filtrationThe precipitated solid was filtered
15. customThe filtrate was collected
16. customthe solvent evaporated
17. additionthe residue treated with diethyl ether/hexanes as before
18. customto obtain more solid precipitate
19. customdried in vacuo

ORD record

ord-45f173db075745ff901c5ff22fc80ca1

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268859B2