trimethylsilylmethanethiol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B) by a procedure similar to the one described in Example 300, Step A, replacing benzenethiol with the appropriate amount of (trimethylsilyl)methanethiol.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B) by a procedure similar to the one described in Example 300, Step A, replacing benzenethiol with the appropriate amount of (trimethylsilyl)methanethiol.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B) by a procedure similar to the one described in Example 300, Step A, replacing benzenethiol with the appropriate amount of (trimethylsilyl)methanethiol.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a clear solution of (2S,4R)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (2.59 g, 6.00 mmol) and trimethylsilylmethanethiol (1.019 mL, 7.20 mmol) in Acetonitrile (30 mL) was added Scandium(III) trifluoromethanesulfonate (0.295 g, 0.600 mmol) as solid by one portion at room temperature. The formed pink solution was stirred at this temperature for 26 h. TLC analysis showed starting material was completely consumed. Quenched with sat. ammonium chloride, extracted with EtOAc. Washed the organic with brine, dried over MgSO4, filtered, evaporated in vacuo. The residue was purified by BIOTAGE® column, eluted with gradient 5˜40% EtOAc-hexane to afford the mixture of diastereomers 3.10 g (97%). This oily mixture was purified by BIOTAGE® again, eluted with gradient 0˜20% EtOAc-toluene to yield the by-product (2S,4S)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-((trimethylsilyl)methylthio)pyrrolidine-1,2-dicarboxylate (1.40 g, 2.62 mmol, 43.7% yield) as a wax and the desired product (2S,4R)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-((trimethylsilyl)methylthio)pyrrolidine-1,2-dicarboxylate (1.25 g, 2.108 mmol, 35.1% yield) as a white foam. 1H NMR (500 MHz, CHLOROFORM-d) ppm −0.03 (s, 9H), 1.33 (dd, J=28.08, 11.29 Hz, 1H), 1.49 (dd, J=17.70, 11.29 Hz, 1H), 2.62-2.85 (m, 2H), 3.62, 3.77 (s, 3H), 3.97 (t, J=11.60 Hz, 1H), 4.16 (dd, J=74.62, 11.44 Hz, 1H), 4.35-4.56 (m, 1H), 4.99-5.19 (m, 1H), 5.17-5.27 (m, 1H), 7.27-7.40 (m, 8H), 7.39-7.49 (m, 2H), 7.49-7.67 (m, 4H). LC-MS (retention time: 3.62 mm, method B), MS m/z 534 (M+H). was completely consumed Quenched with sat. ammonium chloride extracted with EtOAc Washed the organic with brine dried over MgSO4 filtered evaporated in vacuo The residue was purified by BIOTAGE® column eluted with gradient 5˜40% EtOAc-hexane to afford the mixture of diastereomers 3.10 g (97%) This oily mixture was purified by BIOTAGE® again eluted with gradient 0˜20% EtOAc-toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a clear solution of (2S,4R)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (2.59 g, 6.00 mmol) and trimethylsilylmethanethiol (1.019 mL, 7.20 mmol) in Acetonitrile (30 mL) was added Scandium(III) trifluoromethanesulfonate (0.295 g, 0.600 mmol) as solid by one portion at room temperature. The formed pink solution was stirred at this temperature for 26 h. TLC analysis showed starting material was completely consumed. Quenched with sat. ammonium chloride, extracted with EtOAc. Washed the organic with brine, dried over MgSO4, filtered, evaporated in vacuo. The residue was purified by BIOTAGE® column, eluted with gradient 5˜40% EtOAc-hexane to afford the mixture of diastereomers 3.10 g (97%). This oily mixture was purified by BIOTAGE® again, eluted with gradient 0˜20% EtOAc-toluene to yield the by-product (2S,4S)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-((trimethylsilyl)methylthio)pyrrolidine-1,2-dicarboxylate (1.40 g, 2.62 mmol, 43.7% yield) as a wax and the desired product (2S,4R)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-((trimethylsilyl)methylthio)pyrrolidine-1,2-dicarboxylate (1.25 g, 2.108 mmol, 35.1% yield) as a white foam. 1H NMR (500 MHz, CHLOROFORM-d) ppm −0.03 (s, 9H), 1.33 (dd, J=28.08, 11.29 Hz, 1H), 1.49 (dd, J=17.70, 11.29 Hz, 1H), 2.62-2.85 (m, 2H), 3.62, 3.77 (s, 3H), 3.97 (t, J=11.60 Hz, 1H), 4.16 (dd, J=74.62, 11.44 Hz, 1H), 4.35-4.56 (m, 1H), 4.99-5.19 (m, 1H), 5.17-5.27 (m, 1H), 7.27-7.40 (m, 8H), 7.39-7.49 (m, 2H), 7.49-7.67 (m, 4H). LC-MS (retention time: 3.62 mm, method B), MS m/z 534 (M+H). was completely consumed Quenched with sat. ammonium chloride extracted with EtOAc Washed the organic with brine dried over MgSO4 filtered evaporated in vacuo The residue was purified by BIOTAGE® column eluted with gradient 5˜40% EtOAc-hexane to afford the mixture of diastereomers 3.10 g (97%) This oily mixture was purified by BIOTAGE® again eluted with gradient 0˜20% EtOAc-toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.5 g of 1-(6-chloro-3-pyridylmethyl)-2-nitromethyleneimidazolidine, 0.18 g of 37% formaldehyde aqueous solution and 0.24 g of mercaptomethyl trimethylsilane were added to 15 ml of ethanol, and were reacted under reflux for 1 hour. After completing the reaction, the reaction liquor was cooled by ice to precipitate a crystal. The crystal thus precipitated was taken out by filtration, and was washed with a cold ethanol to obtain 0.3 g of the aimed product (Compound No. 20) having a melting point of from 162.3° to 164.3° C. were reacted under reflux for 1 hour the reaction the reaction liquor was cooled by ice to precipitate a crystal The crystal thus precipitated was taken out by filtration was washed with a cold ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B) by a procedure similar to the one described in Example 300, Step A, replacing benzenethiol with the appropriate amount of (trimethylsilyl)methanethiol.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B) by a procedure similar to the one described in Example 300, Step A, replacing benzenethiol with the appropriate amount of (trimethylsilyl)methanethiol.