Dimethyl Sulfate → 6-Cyclohexyl-4-Methyl-5-Phenyl-4h-Thieno[3,2-B]pyrrole-2-Carboxylic Acid

A solution (0.1 M) of methyl 6-cyclohexyl-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylate in THF at 0° C. was treated with NaH (4 eq., 60% dispersion in mineral oil), and the suspension was stirred at RT for 30 min then it was treated dimethyl sulfate (3 eq.). The mixture was stirred at RT for 2 h then it was quenched with water and extracted with AcOEt. The combined organic phase was washed with aqueous NaHCO3 (saturated solution) then dried. Evaporation of the solvent gave a residue that was dissolved in MeOH. The resulting solution (0.13 M) was treated with aqueous NaOH (2 N solution, 8 eq.) then the mixture was heated to reflux for 2 h. After cooling down, the mixture was concentrated and the residue was purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 5 micron, 19×150 mm; flow: 18 mL/min; Gradient: A: H2O+0.05% TFA; B: MeCN+0.05% TFA; 95% A linear to 90% A in 2 min, linear to 60% A in 2 min, linear to 40% in 2 min, linear to 30% A in 2 min, linear to 0% A in 2 min) to afford the title compound (42%) as a solid.

1. stirringThe mixture was stirred at RT for 2 h
2. customit was quenched with water
3. extractionextracted with AcOEt
4. washThe combined organic phase was washed with aqueous NaHCO3 (saturated solution)
5. customthen dried
6. customEvaporation of the solvent
7. customgave a residue that
8. temperaturethe mixture was heated
9. temperatureto reflux for 2 h
10. temperatureAfter cooling down
11. concentrationthe mixture was concentrated
12. customthe residue was purified by RP-HPLC (Conditions
13. wait95% A linear to 90% A in 2 min
14. waitlinear to 60% A in 2 min
15. waitlinear to 40% in 2 min
16. waitlinear to 30% A in 2 min

ORD record

ord-a2697338598243f99310687f7fa44994

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07781431B2