PCZOHLXUXFIOCF-SGFUJYLFSA-N synthesis

Yield:237073-61-9 92%

Reaction Conditions:

in water;acetic acid;

Steps:

1 Preparation of 6(R)-[2-[8(S)-(2-methylbutyryloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]-ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one (Formula I, R1 =H).

EXAMPLE-1 Preparation of 6(R)-[2-[8(S)-(2-methylbutyryloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]-ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one (Formula I, R₁ =H). Ammonium-7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R),dimethyl-8(S)-(2-methylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoate (Formula II, R₁ =H) (4.5 g, 0.0102 moles) and butylated hydroxy toluene (15 mg) were dissolved in glacial acetic acid (27 ml) and stirred under nitrogen atmosphere for 5 hrs. at 35-38° C. After 5 hrs. when the reaction was nearly complete, water (64 ml) was added dropwise over 30 mins. at 30-32° C. The crystallized product was further stirred at this temperature for 30 mins. and then cooled to 15° C. The product was filtered and washed with water (15 ml*3) to remove the traces of acetic acid. Drying in vacuo at 40-42° C. afforded the title compound as a white crystalline material (3.82 g) in 92% yield and about 98% HPLC purity.

References:

US5917058,1999,A