Cyclobutanecarboxylic acid, 3,3-dimethoxy- (9CI) synthesis

Yield:-

Reaction Conditions:

Stage #1:3,3-dimethoxycyclobutanecarboxylic acid methyl ester with sodium hydroxide;water in methanol at 20;
Stage #2: with citric acid in methanol;diethyl ether;waterProduct distribution / selectivity;

Steps:

6.1; 9.1
A solution of NaOH (228 mg, 5.7 mmol) in H₂O (5.7 ml) was added to methyl 3,3-dimethoxycyclobutanecarboxylate (1 g, 5.7 mmol) in MeOH (11.4 ml) and stirred for 30 minutes. The reaction mixture was subsequently diluted with diethyl ether (30 ml), then neutralized and washed with 10% aqueous citric acid solution (1×20 ml). The organic phase was separated, dried over sodium sulfate, filtered and concentrated to furnish 886 mg of a colorless oil.; Step 1: To a solution of methyl 3,3-dimethoxycyclobutanecarboxylate (1.74 g, 10 mmol) in 2:1 MeOH:Water (30 mL) was added solid NaOH (2.5 g, 62 mmol) and the mixture stirred at RT overnight. The mixture was poured into 1:1 ether:citric acid in water (100 mL) and the layers separated. Organic phase was washed with water and brine, then was dried, filtered, and concentrated to give 1.0 g of a colorless solid.

References:

Pfizer Inc US2008/280879, 2008, A1 Location in patent:Page/Page column 22; 23