Water → 3-Phenylpropane-1-thiol

To a solution of 3-phenylpropylbromide (1.08 g) in ethanol (8 ml) was added sodium hydrosulfide (0.871 g), and the mixture was stirred at room temperature for 20 hr. Water was added to the reaction mixture, extracted with diethyl ether, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give 3-phenylpropanethiol. To a solution of the obtained 3-phenylpropanethiol in dioxane (15 ml) were added compound 227-1 (500 mg), diisopropylamine (0.327 ml), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (27 mg) And tris(dibenzylideneacetone)palladium(0)-chloroform adduct (24 mg), and the mixture was stirred at 120° C. for 2 days. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give a mixture of (2,2-dimethyl-5-{2-[4-(3-phenylpropylthio)-3-trifluoromethylphenyl]ethyl}-1,3-dioxan-5-yl)carbamic acid t-butyl ester and a starting material (Compound 227-1). Again, 3-phenylpropanethiol in the same amount as the above was prepared, and the above-mentioned operation was repeated using the mixture of (2,2-dimethyl-5-{2-[4-(3-phenylpropylthio)-3-trifluoromethylphenyl]ethyl}-1,3-dioxan-5-yl)carbamic acid t-butyl ester and the starting material obtained above instead of compound 227-1 to give (2,2-dimethyl-5-{2-[4-(3-phenylpropylthio)-3-trifluoromethylphenyl]ethyl}-1,3-dioxan-5-yl)carbamic acid t-butyl ester as a pale-yellow oil. The pale-yellow oil was dissolved in ethanol (15 ml), concentrated hydrochloric acid (1.5 ml) was added, and the mixture was stirred at 80° C. for 1 hr. The reaction mixture was concentrated, the residue was washed with diethyl ether to give a pale-yellow solid. The pale-yellow solid was purified by HPLC, the obtained residue was converted to hydrochloride by adding hydrogen chloride containing ether (1 mol/l, 15 ml), and the precipitate was collected by filtration and dried to give the object product (90 mg) as a white powder.

1. extractionextracted with diethyl ether
2. washwashed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure

ORD record

ord-0f4f35f8fe024b5db0840aed13300f0a

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129361B2