1-Azaspiro[4.5]dec-7-ene-7-carboxylic acid, 8-hydroxy-2-oxo-, Methyl ester synthesis

Yield:749861-28-7 62.8 %

Reaction Conditions:

with sodium hydride in methanol;mineral oil;benzene at 90;

Steps:

B-15.3 Synthesis of methyl 8-hydroxy-2-1-azaspiro(4,5)dec-7-ene-7-carboxylate

To a stuffed solution of dimethyl 3, 3’-(5-oxopyrrolidine-2, 2-diyldipropionate) (40 g, 155.6 mmol) in benzene (300 ml) at 0 °C was added Methanol (0.6 ml, 15.56 mmol) followed by sodium hydride (60% in oil, 15.5 g, 389.10 mmol). After stuffing at 90 °C for 30 mm, aqueous 3N HC1 was added and the mixture was extracted with ethyl acetate (3x200 ml). The combined organic layer was washed with saturated aqueous sodium bicarbonate solution and brine then dried over anhydrous sodium sulphate. The solvent was removed under reduced pressure. Resulting solid residue was triturated with hexane to afford the ketoester title compound (62.8%) as a white solid. ‘H-NMR (400 MHz, CDC13) & 12.16 (s, 1H) 6.270 (br, 1H), 3.74 (s, 3H), 2.52-2.31 (m, 6H), 2.19-1.90 (m, 4H).

References:

WO2016/44626,2016,A1 Location in patent:Paragraph 00361