Iodine → 1-(Benzo[b]thiophen-4-yl)-2-chloroethan-1-one

Temperature

55 °C

To a suspension of magnesium turnings (0.41 g) in tetrahydrofuran (5 ml) under nitrogen were added 1 ml of a solution of 4-bromobenzo[b]thiophene (3.45 g, prepared in a manner similar to that described in Bull. Soc. Chim. Fr., 1966, 11, 3667) in tetrahydrofuran (15 ml) and a crystal of iodine. The mixture was stirred at 50-60° C. and once the reaction had initiated the rest of the bromobenzo[b]thiophene solution was added dropwise at 50-60° C. over 10 minutes. The mixture was stirred for a further 0.5 hour at 50-60° C. then cooled to 0° C. A solution of 2-chloro-N-methoxy-N-methylacetamide (2.2 g) in tetrahydrofuran (20 ml) was added dropwise at 0-5° C. over 15 minutes and the mixture was stirred at 0-5° C. for 1 hour. Saturated aqueous ammonium chloride solution (25 ml) was added, the mixture was stirred at ambient temperature for 10 minutes, then the aqueous layer was separated and shaken with ethyl acetate (50 ml). The combined organic phases were dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by flash chromatography over silica using a 19:1 mixture of petroleum ether (b.p. 60-80° C.) and ethyl acetate as eluant. Appropriate fractions were combined and the solvents removed in vacuo to give 1-(benzo[b]thiophen-4-yl)-2-chloroethan-1-one (1.15 g) as a pale yellow oil which was used without further purification.

1. customprepared in a manner similar to
2. additionwas added dropwise at 50-60° C. over 10 minutes
3. stirringThe mixture was stirred for a further 0.5 hour at 50-60° C.
4. temperaturethen cooled to 0° C
5. stirringthe mixture was stirred at 0-5° C. for 1 hour
6. stirringthe mixture was stirred at ambient temperature for 10 minutes
7. customthe aqueous layer was separated
8. stirringshaken with ethyl acetate (50 ml)
9. dry with materialThe combined organic phases were dried (MgSO4)
10. customthe solvents were removed in vacuo
11. customThe residue was purified by flash chromatography over silica using
12. additiona 19:1 mixture of petroleum ether (b.p. 60-80° C.) and ethyl acetate as eluant
13. customthe solvents removed in vacuo

ORD record

ord-a06d8b66dee14d3096750ddd3c7d64c3

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06900216B2