Spiro[2.3]hexane-1-carboxylic acid, 1-amino-, methyl ester synthesis

Yield:-

Reaction Conditions:

with diphenyl phosphoryl azide;triethylamine in tert-butyl alcohol; for 21 h;Heating / reflux;

Steps:

A.I.6.3

To a mixture of spiro [2,3] hexane-1, 1-dicarboxylic acid methyl ester (660 mg, 3.58 mmol) in 3 mL of anhydrous t-BuOH was added 1.08 g (3.92 mmol) of DPPA and 440 mg (4. 35 mmol) of Et3N. The mixture was heated at reflux for 21 h and then partitioned between H20 and ether. The ether phase was dried over magnesium sulfate, filtered and concentrated in vacuo to yield an oil. To this oil was added 3 mL of a 4'M HCl/dioxane solution. This acidic solution was stirred at rt for 2 h and then concentrated in vacuo. The residue was triturated with ether to give 400 mg (58 %) of desried predict as a white solid. 1H NMR (300 MHz, d6-DMSO) 8 8.96 (br s, 3 H), 3.71 (s, 3 H), 2.41 (m, 1 H), 2.12 (m, 4 H), 1.93 (m, 1 H), 1.56 (q, 2 H, J=8 Hz). LC- MS of free amine: MS m/z 156 (M++1).

References:

WO2005/51410,2005,A1 Location in patent:Page/Page column 71