91312-53-7

Upstream product

• 94370-99-7 ethyl (S)-4-(2,2-dimethyl-1,3-dioxolan-4-yl)-3-oxobutanoate 

Downstream Products

• 915201-15-9 ethyl (3R,5S)-3-tert-butyldiphenylsilyloxy-5,6-(isopropylidenedioxy)hexanoate 
• 91312-59-3 (3R,5S)-3-O-(tert-butyldimethylsilyl)-6-(para-tolylsulfonyl)-3,5,6-trihydroxyhexanoic acid δ-lactone 
• 86030-94-6 methyl 3-O-(tert-butyldiphenylsilyl)-2,4-dideoxy-β-D-erythro-hexopyranoside 
• 927211-53-8 (4R,6S)-4-tert-butyldiphenylsilyloxy-6-(p-tosyloxymethyl)tetrahydropyran-2-one 
• 927211-52-7 (4R,6S)-4-tert-butyldiphenylsilyloxy-6-(hydroxymethyl)tetrahydropyran-2-one 
• 116627-67-9 (4R,6S)-trans-4--6-iodomethyltetrahydropyran-2-one 
• 915201-19-3 (2R,4R,6R)-2-(2-aminoethyl)-4-tert-butyldiphenylsilyloxy-6-methoxytetrahydropyran 
• 915201-18-2 (2R,4R,6R)-4-tert-butyldiphenylsilyloxy-2-cyanomethyl-6-methoxytetrahydropyran 
• 915201-17-1 (2S,4R,6S)-2-(p-chlorobenzenesulfonyloxy)methyl-4-tert-butyldiphenylsilyloxy-6-methoxytetrahydropyran 
• 915201-16-0 (3R,5S)-3-tert-butyldiphenylsilyloxy-5,6-(isopropylidenedioxy)hexanal 
• 91327-64-9 (3S,5S)-3-O-(tert-butyldimethylsilyl)-6-(para-tolylsulfonyl)-3,5,6-trihydroxyhexanoic acid δ-lactone 

Relevant academic research and scientific papers

Synthesis and highly stereoselective hydrogenation of the statin precursor ethyl (5S)-5,6-isopropylidenedioxy-3-oxohexanoate

A search for the large-scale preparation of (5S)-5,6-(isopropylidenedioxy)- 3-oxohexanoates (2) - a key intermediate in the synthesis of pharmacologially important statins - starting from (S)-malic acid is described. The synthesis of the required initial compound methyl (3S)-3,4-(isopropylidenedioxy)butanoate (1) by Moriwake's reduction of dimethyl (S)-malate (3) has been improved. Direct 2-C chain elongation of ester 1 using the lithium enolate of tert-butyl acetate has been shown to be successful at a 3- to 5-fold excess of the enolate. Unfortunately, the product, tert-butyl (5S)-5,6-(isopropylidenedioxy)-3- oxohexanoate (2a) is unstable during distillation. Ethyl (5S)-5,6- (isopropylidenedioxy)-3-oxohexanoate (2b) was prepared alternatively on a multigram scale from (3S)-3,4-(isopropylidenedioxy)butanoic acid (7) by activation with N,N′-carbonyldiimidazole and subsequent reaction with Mg(OOCCH2COOEt)2. A convenient pathway for the in situ preparation of the latter is also described. Ethyl ester (2b) can be advantageously purified by distillation. The stereochemistry of the catalytic hydrogenation of β-keto ester (2b) to ethyl (55)-5,6-(isopropylidenedioxy)- 3-hydrohyhexanoate (syn-6 and anti-6) has been studied using a number of homogeneous achiral and chiral Rh(I) and Ru(II) complexes with phosphine ligands. A comparison of Rh(I) and Ru(II) catalysts with (S)- and (R)-BINAP as chiral ligands revealed opposite activity in dependence on the polarity of the solvent. No influence of the chiral backbone of substrate 2b on the enantioselectivity was noted. A ratio of syn-6/anti-6 = 2.3 was observed with an achiral (Ph3P)3RuCl2 catalyst. Ru[(R)-Tol-BINAP]Cl2 neutralized with one equivalent of AcONa afforded the most efficient catalytic system for the production of optically pure syn-(5S)-5,6-isopropylidenedioxy-3-hydroxyhexanoate (syn-6) at a preparative substrate/catalyst ratio of 1000:1.