(1S,2S)-2-(((1R,2S,5R)-2-isopropyl-5-Methylcyclohexyloxy)carbonyl)cyclopropanecarboxylic acid synthesis

Yield:175221-03-1 69%

Reaction Conditions:

with sodium hydroxide in isopropyl alcohol at 70; for 16 h;

Steps:

1.c ( 1S,2A)-Cyclopropanc-1 ,2-dicarboxyl ic acid mono-ff 1 /?,2S,5/?)-2-isopropyl-5-mcthyl- cyclohexyl) ester

To a solution of l,2-bis(l7?,25',57?)-5-methyl-2-(propan-2-yl)cyclohexyl ( 1 S,2S)- cyclopropane-l,2-dicarboxylate (25 g, 61.58 mmol) in isopropanol (250 mL) was added a 5 M solution of NaOH (13.54 mL, 67.73 mmol) at 25 °C. The mixture was stirred at 70 °C for 16 h. The organic solvent was removed under reduced pressure. Water (200 mL) was added and the mixture was washed with diethyl ether (2 x 150 mL).The aqueous layer was acidified with 2 N HC1 (pH ~2) and extracted with ethyl acetate (3 x 250 mL). The combined organic layers were dried over Na2S0₄, filtered and concentrated under reduced pressure to get ( 1 S,2S)-2-( j [( 1 /?,2S,5/?)-5-mcthyl-2-(propan-2- yl)cyclohexyl]oxy}carbonyl)cyclopropane-l -carboxylic acid (11.4 g, 69%) as off white semisolid.

References:

WO2020/2314,2020,A1 Location in patent:Page/Page column 15; 17