Reaction #894

Reaction equation

Hydrochloric acid

n-butyllithium

6-Bromo-3,4-dihydro-4,4,5,8-tetramethyl-2H-1-benzothiopyran

Dimethylformamide

→

desired compound

3,4-Dihydro-4,4,5,8-tetramethyl-2H-1-benzothiopyran-6-carboxaldehyde

Solvents

diethyl ether

Conditions

Workup

1. 1
   Temperaturecooled in a dry-ice/acetone bath
2. 2
   Temperatureto warm to -40° C
3. 3
   Temperatureto warm to 23° C
4. 4
   OtherThe organic phase was separated
5. 5
   Washwashed with saturated aqueous sodium bicarbonate solution (100 mL)
6. 6
   DryingThe organic phase was dried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Otherevaporated under reduced pressure

Procedure

6-Bromo-3,4-dihydro-4,4,5,8-tetramethyl-2H-1-benzothiopyran (19.8 g, World Patent Application 95/04054) was dissolved in diethyl ether (350 mL) and treated with n-butyllithium (2.5N in hexanes, 42 mL). The mixture was stirred at room temperature for 1 h and then cooled in a dry-ice/acetone bath. Dimethylformamide (16 mL) was added over a period of several minutes and the reaction bath was allowed to warm to -40° C. Hydrochloric acid (1N aqueous, 100 mL) was added and the mixture was allowed to warm to 23° C. The organic phase was separated and washed with saturated aqueous sodium bicarbonate solution (100 mL). The organic phase was dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using hexanes/ether (9:1) as eluent to afford the desired compound as a yellow semi-solid (7.7 g). 1H NMR(CDCl3): δ 1.5 (6H), 2.0 (2H), 2.3 (3H), 2.8 (3H), 3.0 (2H), 7.4 (1H), 10.2 (1H).

Source