Chloroacetone → 5-Bromo-3-methyl-1-benzothiophene

A mixture of 4-bromothiophenol (3.9 g, 20 mmol), K2CO3 (5.5 g, 40 mmol) and chloroacetone (6.6 mL, 82 mmol) in acetone (50 mL) was heated at reflux over night. The reaction mixture was filtered and the solvent was evaporated giving 5.0 g crude product. The intermediate thioether was dissolved in chlorobenzene (50 mL) and polyphosphoric acid (PPA, 2.5 g) was added (Plé et al., (1988) J. Heterocyclic Chem. 25, 1271-1272). After reflux for 24 h, the solvent was decanted and the PPA residue was treated with CH2Cl2. The combined organic extracts were washed with water and dried. Evaporation of the solvents afforded the crude product which was purified on silica (heptane as eluent) to give the title compound (2.36 g, 50% over two steps). 1H NMR (400 MHz, CDCl3) δ ppm 2.41 (d, J=1.20 Hz, 3 H) 7.11 (qd, J=1.20, 0.54 Hz, 1 H) 7.44 (ddd, J=8.53, 1.90, 0.54 Hz, 1 H) 7.70 (dd, J=8.53, 0.54 Hz, 1 H) 7.85 (dd, J=1.90, 0.54 Hz, 1 H).

1. temperaturewas heated
2. temperatureat reflux over night
3. filtrationThe reaction mixture was filtered
4. customthe solvent was evaporated
5. customgiving 5.0 g crude product
6. temperatureAfter reflux for 24 h
7. customthe solvent was decanted
8. additionthe PPA residue was treated with CH2Cl2
9. washThe combined organic extracts were washed with water
10. customdried
11. customEvaporation of the solvents
12. customafforded the crude product which
13. customwas purified on silica (heptane as eluent)

ORD record

ord-1073c627441140b7b2c0772ca78c6778

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233946B2