(1R,3S)-1,3-Cyclohexanedicarboxylic Acid 1-Ethylester synthesis

Yield:227783-08-6 100%

Reaction Conditions:

Stage #1: cis-1,3-Cyclohexanedicarboxylic acid diethyl ester;lipase AY₃₀ in water at 20; pH=7.2; for 30 h;Aqueous phophate buffer;
Stage #2: with hydrogenchloride in water; pH=< 2;

Steps:

4 Preparation 4;1,3-cyclohexanedicarboxylic acid, monoethyl ester (1R, 3S)

To a suspension of compound from preparation 3 (40 g, 17.5 mmol) in PH 7.2 phosphate buffer [0.2 M] (1.2 l) was added lipase AY30 (Amano, 16.7 g).The mixture was stirred vigorously at room temperature for 30 hours.The mixture was acidified with 10-15% HCl to PH<2, and extracted with ethyl acetate (500 ml*2).The combined organic solution was washed with aqueous 10% Na2CO3 (100 ml*2) and water (100 ml*2).The combined aqueous layers were washed again with ethyl acetate (150 ml) and then acidified with 10-15% HCl to PH<2.The acidified aqueous was then extracted with ethyl acetate (150 ml*3).The combined organic solution was dried over MgSO4.After filtration and concentration the title compound (35.6 g, 100% yield) was obtained. 1H NMR (500 MHz, CDCl3) δ 4.12 (q, J=7.0 Hz, 2H), 2.20-2.40 (m, 3H), 1.85-2.05 (m, 3H), 1.5 (q, 2H), 1.35 (m, 2 H), 1.24 (t, J=7.0 Hz, 3H).[α]D +3.2°, [α]365 +10.4° (c, 0.434; CHCl3).[α]D+3.0°, [α]365 +9.6° (c, 0.532; CH3OH).

References:

US2004/10005,2004,A1 Location in patent:Page 18