Water → HCID 67191222, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1,1,1,3,3,3-Hexamethyldisilazane (1.81 g, 11.19 mmol) in tetrahydrofuran (15 mL) cooled to −20° C. under nitrogen was added n-butylithium (6.4 mL of a 1.6 M solution, 10.21 mmol) slowly keeping the temperature at −20° C. for 30 min. N-((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-2-(3-methylsulfanyl-phenyl)-acetamide (1.60 g, 4.86 mmol) in tetrahydrofuran (15 mL) was added slowly to the reaction maintaining the temperature at −20° C. After the addition was complete the reaction was warmed to 0° C. and stirred for 30 min. A solution of 2,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.31 g, 10.21 mmol) and iodomethylcyclopentane (prepared in PCT WO2004/052869 A1 Example 1, 1.23 g, 5.84 mmol) were added to the reaction at 0° C. and stirring continued for 3 h. The reaction was poured into water (60 mL) and extracted with ethyl acetate. The ethyl acetate fractions were washed with water, 2 N aqueous hydrochloric acid solution, saturated sodium bicarbonate and saturated sodium chloride solution and then dried over magnesium sulfate. Filtration and concentration afforded the crude product which was purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) to yield (R)-3-cyclopentyl-N-((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-2-(3-methylsulfanyl-phenyl)-propionamide (1.16 g, 58%) as a clear sticky solid.

Provenance & Evidence