tert-BUTYL CHLORIDE → Methyl 5-(tert-butyl)-3-methylthiophene-2-carboxylate

Temperature

-78 °C

A solution of methyl 3-methylthiophene-2-carboxylate 109a (33 g, 0.211 mol) in dry CH2Cl2 (30 mL) was added dropwise to a mixture of aluminum chloride (40 g, 0.297 mol) and dry CH2Cl2 (200 mL) at −78° C., under nitrogen. The reaction mixture was stirred for 10 min at −78° C., and a solution of tert-butyl chloride (23 mL, 0.211 mol) in dry CH2Cl2 (30 mL) was added dropwise at −78° C. The reaction mixture was stirred for 1 h at −78° C., gradually allowed to warm to room temperature and stirred for 16 h at room temperature. It was poured on ice and extracted with CH2Cl2 (2×200 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent evaporated under vacuum. The obtained residue was purified by fractional distillation to yield methyl 5-tert-butyl-3-methylthiophene-2-carboxylate 109b (19 g, 43%) as a light yellow liquid.

1. stirringThe reaction mixture was stirred for 1 h at −78° C.
2. temperatureto warm to room temperature
3. stirringstirred for 16 h at room temperature
4. additionIt was poured on ice
5. extractionextracted with CH2Cl2 (2×200 mL)
6. dry with materialThe organic layer was dried over anhydrous Na2SO4
7. customthe solvent evaporated under vacuum
8. distillationThe obtained residue was purified by fractional distillation

ORD record

ord-cdd5fc66ced34564bf77c6409c16ed63

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08975260B2