| abstract |
Preparation of simvastatin (6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)2-(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydro-1(S)-naphthyl]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one) of formula (I) comprises: (a) treating a naphthyl ester with an alkyl amine of to give a naphthyl amide; (b) treating the amide with an alkali metal amide and then dried alkyl halide to give a methylated naphthyl amide; (c) hydrolysing the amide linkage and closing the open pyranone ring without protecting or deprotecting the two hydroxy groups of the ring, by treating with a strong base followed by treatment with ammonium hydroxide to give an ammonium salt; (d) relactonizing the salt by heating in a solvent to give (I). R2 = H, Na, K or NH4; R3 = 3-6C n-alkyl or cycloalkyl. |