Trifluoroacetic acid → HCID 178526001, compound

Trans-4-(4-trifluoromethylsulfanyl-phenylamino)-cyclohexanol (160 mg, 0.55 mmol, prepared in accordance with Example 29) was placed under an inert atmosphere and dissolved in dry tetrahydrofuran (2 mL). A molar solution of lithium bis(trimethylsilyl)-amide (1 mL, 1.0 mmol) was added. After 15 min, tert-butyl-bromoacetate (75 μL, 0.55 mmol) was added. After two additional hours, more lithium bis-(trimethylsilyl)-amide solution (500 μL, 0.50 mmol) and tert-butyl-bromoacetate (37 μL, 0.28 mmol) was added. After 4 hr, the mixture was diluted with diethylether (20 mL), washed with water (10 mL), and washed with saturated aqueous hydrogencarbonate (10 mL). The organic layer was collected, dried over magnesium sulfate, filtered, and concentrated under vacuum to afford an oil. This crude product was diluted in dichloromethane (4 mL) and treated with trifluoroacetic acid (3 mL) at room temperature. After 3 hr, the mixture was diluted with diethylether (20 mL) and washed with water (3×10 mL), and washed with aqueous saturated hydrogencarbonate (2×10 mL). The organic layer was collected, dried over magnesium sulfate, filtered, and concentrated under vacuum. The oily residue obtained was purified by column chromatography on silica gel (dichloromethane followed by dichloromethane/methanol, 95:5). The desired product was isolated as a yellow solid (68 mg, 35% yield).

1. waitAfter 4 hr
2. washwashed with water (10 mL)
3. washwashed with saturated aqueous hydrogencarbonate (10 mL)
4. customThe organic layer was collected
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated under vacuum
8. customto afford an oil
9. waitAfter 3 hr
10. washwashed with water (3×10 mL)
11. washwashed with aqueous saturated hydrogencarbonate (2×10 mL)
12. customThe organic layer was collected
13. dry with materialdried over magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated under vacuum
16. customThe oily residue obtained
17. customwas purified by column chromatography on silica gel (dichloromethane followed by dichloromethane/methanol, 95:5)

ORD record

ord-3b67d3f17ddd4cd989893646c9ffd740

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569495B2