5-[(TERT-BUTOXYCARBONYL)AMINO]BICYCLO[3.1.1]HEPTANE-1-CARBOXYLIC ACID synthesis

Yield:1035325-28-0 85%

Reaction Conditions:

Stage #1: 5-tert-butoxycarbonylamino-bicyclo[3.1.1]heptane-1-carboxylic acid methyl esterwith lithium hydroxide;water in methanol at 0; for 48 h;
Stage #2: with citric acid in water;pentane; pH=5;

Steps:

51

5-tert-Butoxycarbonylamino-bicyclo[3.1.1]heptane-1-carboxylic acid. Solid LiOH (2.18 g, 51.98 mmol) was added portion wise to a solution of 5-tert- Butoxycarbonylamino-bicyclo[3.1.1]heptane-1-carboxylic acid methyl ester (3.5 g, 12.09 mmol) in 80 % aqueous MeOH (14 ml) at O⁰C. The reaction mixture was stirred for 48h, evaporated to remove the alcohol. The crude residue was diluted with water, washed with pentane and then acidified with 10 % citric acid (pH-5). It was extracted with dichloromethane, dried over sodium sulfate and evaporated to afford the desired product (2.8 g, 85 %) as an off white solid.¹H NMR (400 MHz, DMSO-d₆): δ 12.2 (br s, 1 H), 6.97 (br s, 1 H), 2.29 (br m, 2H), 1.78 -1.75 (m, 8H), 1.37 (s, 9H).

References:

WO2008/75196,2008,A1 Location in patent:Page/Page column 113