Catechol → Chloromethyl-benzodioxole

5-amino-isoxazole 2 reacts with thiophene-3-sulfonyl chloride 3, in the presence of a base, such as sodium hydride, in an appropriate solvent, such as anhydrous tetrahydrofuran, to give a thiophene-methyl ester, which is then treated with a base, such as sodium hydroxide, to give thiophene-carboxylic acid 4. Catechol 5 is treated with a base, such as cesium carbonate, in appropriate solvents, such dimethylformamide and dichloromethane, at an elevated temperature and under an inert atmosphere, such as nitrogen, to affored benzodioxole 6, which is then reacted with formaldehyde in the presence of an acid, such as hydrochloric acid, and in the presence of a catalyst, such as tetrabutylammonium bromide, in an appropriate solvent, such as ether, to yield chloromethyl-benzodioxole 7. Compound 4 is treated with coupling reagents, such as 1,1′-carbonyldiimidazole and N,O-dimethylhydroxylamine, in the presence of a base, such as imidazole, in an appropriate solvent, such as anhydrous tetrahydrofuran, to make a weinreb amide intermediate, which is then reacted with a Grignard reagent formed from compound 5, in an appropriate solvent, such as anhydrous tetrahydrofuran, to afford thiophene 8 of Formula I.

ORD record

ord-dcd88e013ad94a0b8896d5804b4c2b0c

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863308B2