Yield:-

Reaction Conditions:

Stage #1: di-tert-butyl 2,6-diazaspiro[3.3]heptane-2,6-dicarboxylatewith methanol;acetyl chloride at 20; for 20 h;Inert atmosphere;
Stage #2: with potassium hydroxide in methanol at 30;
Stage #3: oxalic acid in diethyl ether at 20; for 1 h;

Steps:

4.4

fer/-Butyl 2.6-diazaspiro[3 31heptane-2-carboxylate oxalate; Into a 5 L, 3 -neck, round bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a solution of acetyl chloride (25 3 g, 322 3 mmol) in methanol (2 7 L) To this was added di-tert-buty 2,6-diazaspiro[3 3]heptane-2,6-dicarboxylate (96 g, 321 mmol) The resulting solution was stirred for 20 h while the temperature was20 maintained at 20 ⁰C Solid KOH (18 1 g, 323 2 mmol) was added in small portions in order to maintain the temperature below 30 ⁰C The resulting mixture was concentrated under reduced pressure The residue was transferred to a separatory funnel using water (200 mL) and EtOAc (1 L) The aqueous layer was extracted with EtOAc (2 x 500 mL) The combined organic layers were dried over Na₂Sθ₄ and concentrated under reduced pressure To the residue was added 1 L25 of ether and oxalic acid (28 9 g, 321 mmol) The resulting solution was stirred for 1 h at room temperature The resulting solid was collected by vacuum filtration, washed once with EtOAc (500 mL) and once with ether (1 L) to give the title compound as a white solid 1H NMR (400 MHz, D₂O) 5 4 20 (4H, s), 4 07 (4H, s), 1 31 (9H, s) MS (ESI, Q⁺) m/z 199 (M + 1)

References:

WO2010/108268,2010,A1 Location in patent:Page/Page column 69