Diisopropylamine → Methyl 4-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-5-carboxylate

Temperature

-78 °C

n-Butyl lithium (2.5 M, 15.8 mL) is added dropwise via syringe to a solution of diisopropyl amine (55 mL) in anhydrous THF (20 mL) at −10° C. under an atmosphere of nitrogen. After stirring for 30 min at this temperature, the solution is cooled to −78° C. and a solution of containing 6,7-dihydro-1-benzthiophen-4(5H)one (BI.1, 5.00 g) in anhydrous THF (20 mL) is added dropwise over 15 minutes. The solution is warmed to 0° C. and stirred for one hour at that temperature. After re-cooling to −78° C., HMPA (5.7 mL) and methyl-cyanoformate (3.1 mL) are sequentially added. The solution is stirred for 10 minutes at −78° C. The reaction mixture is quickly poured into cold water (100 mL) and extracted with ether (250 mL). The organic phase is washed with brine, dried over Na2SO4, filtered, and concentrated to give a red oil. This oil is chromatographed on a Biotage column eluting with 0-30% ethyl acetate in heptane (500 mL each 10%) to give 3.87 g (56%) of the title compound as a white solid. Physical characteristics. Mp. 85-86° C.; MS (ESI+) m/z 211.0 (M+H)+; HRMS (FAB) m/z 211.0425 (C10H10O3S+H). Anal. Found: C, 57.15; H, 4.84.

1. temperatureThe solution is warmed to 0° C.
2. stirringstirred for one hour at that temperature
3. temperatureAfter re-cooling to −78° C.
4. stirringThe solution is stirred for 10 minutes at −78° C
5. extractionextracted with ether (250 mL)
6. washThe organic phase is washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a red oil
11. customThis oil is chromatographed on a Biotage column
12. washeluting with 0-30% ethyl acetate in heptane (500 mL each 10%)

ORD record

ord-d13459d3b2dd48b6bbfec423418b96db

Source dataset

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06559145B2