(1S,2S)-cyclohexane-1,2-diol

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (5S)-2-(trans-4-hydroxycyclohexyl)-2,7-diazaspiro[4.5]decan-1-one (20 mg, 0.00007 mol) which was prepared using procedures analogous to those described in the synthesis of example 472-a and followed by standard hydrogenation to remove the carbobenzyloxy (Cbz) protecting group and 2-chloro-1-iodo-4-methylbenzene (22.7 mg, 0.0000831 mol), potassium carbonate (20.1 mg, 0.000145 mol), copper(I) iodide (0.6 mg, 0.000003 mol), and (1S,2S)-cyclohexane-1,2-diol (16.1 mg, 0.000138 mol) in tert-butyl alcohol (1.0 mL, 0.010 mol) was heated at 100° C. for 18 h. The crude product was purified by prep-HPLC to afford the desired product. LC-MS: 377.1 (M+H)+. was prepared those described in the synthesis of example 472-a The crude product was purified by prep-HPLC

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

Procedure: Sodium hydride (7.1 g, 0.3 mol) was dispersed in 200 ml DMF and added with (1S,2S)-cyclohexane-1,2-diol (11.42 g, 98.3 mmol) while cooling with ice. The mixture after being cooled with ice for another one hour was reacted at room temperature for 2 hours and cooled again, followed by addition of p-fluorobenzonitrile (25 g, 206 mmol). After the reaction was continued overnight, the mixture was added carefully with 5 ml water to inactivate excess sodium hydroxide, followed by distillation of DMF in pressure. The residue was added with 200 ml water and then extracted with ethyl acetate, followed by washing with a saturated solution of sodium chloride thereby obtaining a coarse crystalline product. The crystalline product was then recrystallized from 200 ml isopropanol thereby obtaining the intended product (26.2 g, 82.3 mmol, 84%). while cooling with ice The mixture after being cooled with ice for another one hour was reacted at room temperature for 2 hours cooled again followed by distillation of DMF in pressure The residue was added with 200 ml water extracted with ethyl acetate by washing with a saturated solution of sodium chloride thereby obtaining a coarse crystalline product The crystalline product was then recrystallized from 200 ml isopropanol

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

Procedure: Sodium hydride (7.1 g, 0.3 mol) was dispersed in 200 ml DMF and added with (1S,2S)-cyclohexane-1,2-diol (11.42 g, 98.3 mmol) while cooling with ice. The mixture after being cooled with ice for another one hour was reacted at room temperature for 2 hours and cooled again, followed by addition of p-fluorobenzonitrile (25 g, 206 mmol). After the reaction was continued overnight, the mixture was added carefully with 5 ml water to inactivate excess sodium hydroxide, followed by distillation of DMF in pressure. The residue was added with 200 ml water and then extracted with ethyl acetate, followed by washing with a saturated solution of sodium chloride thereby obtaining a coarse crystalline product. The crystalline product was then recrystallized from 200 ml isopropanol thereby obtaining the intended product (26.2 g, 82.3 mmol, 84%). while cooling with ice The mixture after being cooled with ice for another one hour was reacted at room temperature for 2 hours cooled again followed by distillation of DMF in pressure The residue was added with 200 ml water extracted with ethyl acetate by washing with a saturated solution of sodium chloride thereby obtaining a coarse crystalline product The crystalline product was then recrystallized from 200 ml isopropanol

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (5S)-2-(trans-4-hydroxycyclohexyl)-2,7-diazaspiro[4.5]decan-1-one (20 mg, 0.00007 mol) which was prepared using procedures analogous to those described in the synthesis of example 472-a and followed by standard hydrogenation to remove the carbobenzyloxy (Cbz) protecting group and 2-chloro-1-iodo-4-methylbenzene (22.7 mg, 0.0000831 mol), potassium carbonate (20.1 mg, 0.000145 mol), copper(I) iodide (0.6 mg, 0.000003 mol), and (1S,2S)-cyclohexane-1,2-diol (16.1 mg, 0.000138 mol) in tert-butyl alcohol (1.0 mL, 0.010 mol) was heated at 100° C. for 18 h. The crude product was purified by prep-HPLC to afford the desired product. LC-MS: 377.1 (M+H)+. was prepared those described in the synthesis of example 472-a The crude product was purified by prep-HPLC

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (5S)-2-(trans-4-hydroxycyclohexyl)-2,7-diazaspiro[4.5]decan-1-one (20 mg, 0.00007 mol) which was prepared using procedures analogous to those described in the synthesis of example 472-a and followed by standard hydrogenation to remove the carbobenzyloxy (Cbz) protecting group and 2-chloro-1-iodo-4-methylbenzene (22.7 mg, 0.0000831 mol), potassium carbonate (20.1 mg, 0.000145 mol), copper(I) iodide (0.6 mg, 0.000003 mol), and (1S,2S)-cyclohexane-1,2-diol (16.1 mg, 0.000138 mol) in tert-butyl alcohol (1.0 mL, 0.010 mol) was heated at 100° C. for 18 h. The crude product was purified by prep-HPLC to afford the desired product. LC-MS: 377.1 (M+H)+. was prepared those described in the synthesis of example 472-a The crude product was purified by prep-HPLC

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

Procedure: Sodium hydride (7.1 g, 0.3 mol) was dispersed in 200 ml DMF and added with (1S,2S)-cyclohexane-1,2-diol (11.42 g, 98.3 mmol) while cooling with ice. The mixture after being cooled with ice for another one hour was reacted at room temperature for 2 hours and cooled again, followed by addition of p-fluorobenzonitrile (25 g, 206 mmol). After the reaction was continued overnight, the mixture was added carefully with 5 ml water to inactivate excess sodium hydroxide, followed by distillation of DMF in pressure. The residue was added with 200 ml water and then extracted with ethyl acetate, followed by washing with a saturated solution of sodium chloride thereby obtaining a coarse crystalline product. The crystalline product was then recrystallized from 200 ml isopropanol thereby obtaining the intended product (26.2 g, 82.3 mmol, 84%). while cooling with ice The mixture after being cooled with ice for another one hour was reacted at room temperature for 2 hours cooled again followed by distillation of DMF in pressure The residue was added with 200 ml water extracted with ethyl acetate by washing with a saturated solution of sodium chloride thereby obtaining a coarse crystalline product The crystalline product was then recrystallized from 200 ml isopropanol