2-AMINO-5-METHYL-THIOPHENE-3-CARBOXYLIC ACID synthesis

Yield:41940-47-0 87%

Reaction Conditions:

Stage #1: methyl 2-amino-5-methylthiophene-3-carboxylatewith methanol;water;lithium hydroxide in tetrahydrofuran at 85; for 2 h;
Stage #2: with hydrogenchloride in tetrahydrofuran;water;

Steps:

20.1

2-Amino-5-methyl-thiophene-3-carboxylic acid methyl ester (60a, 5.0 g, 29.2 mmol) was placed in a 250 mL round-bottom flask equipped with a stir bar and suspended in 100 mL of a 3:2:1 mixture of THF, MeOH and water. Lithium hydroxide monohydrate was dissolved in 85 mL of water and added to the flask with stirring. The flask was equipped with a condenser and the mixture was heated at 85° C. for 2 h. After cooling, the THF and MeOH were evaporated, EtOAc was added, and the organic and aqueous layers were separated. The aqueous layer was acidified to pH 4 with 1M HCl and extracted with EtOAc. The organic layer was dried (Na₂SO₄), filtered and concentrated to give 4.0 g (87%) of 2-amino-5-methyl thiophene-3-carboxylic acid (60b) which was used without purification: ms [M-H]=156.

References:

US2006/40927,2006,A1 Location in patent:Page/Page column 36