Trimethyl-(2-tributylstannanylmethoxymethoxy-ethyl)-silane → N-{1-[(5-Hydroxy-1-isopropyl-3-methyl-4-oxo-pent-2-enyl)-methyl-carbamoyl]-2,2-dimethyl-propyl}-3-methyl-2-methylamino-3-phenyl-butyramide

Participants

Reaction Conditions

Reaction Steps

To a solution of trimethyl-(2-tributylstannanylmethoxymethoxy-ethyl)-silane (933 mg, 2.07 mmole, E. Fernandez-Megia and S. V. Ley; Synlett 2000, 4, 455-8) in 6 mL tetrahydrofuran at −78° C. is added dropwise 1.6 M n-butyllithium solution in hexanes (1.25 mL, 2.0 mmole). The resulting yellow solution is stirred for 10 mins at −78° C. Then a solution of N,β,β-trimethyl-L-phenylalanyl-N1{(1S,2E)-1-isopropyl-4-[methoxy(methyl)amino]-3-methyl-4-oxobut-2-enyl}-N1,3-dimethyl-L-valinamide (258 mg, 0.5 mmole, Example 52) in tetrahydrofuan (5 mL) at −78° C. is added dropwise and the reaction mixture stirred at −78° C. for 15 mins and then at −60° C. for 45 mins. The reaction is quenched with a saturated aqueous solution of ammonium chloride (2 mL), warmed to room temperature and partioned between ethyl acetate (50 mL) and saturated aqueous solution of ammonium chloride (50 mL). The aqueous layer is extracted with ethyl acetate (30 mL) and the combined organic layer is washed with water, brine, dried over sodium sulfate, filtered and the residue treated with a mixture of trifluoroacetic acid (10 mL) and dichloromethane (5 mL) at 0° C. and stirred for 1 hour, evaporated and then purified by HPLC to give 52 mg of an off-white solid, MS (ES): m/z 488.4 (M+H).

Provenance & Evidence