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

HRID 505785Notes

Reaction equation

HRID 505785 reaction equation
[CH:1]1([C:7]2[C:8]3[S:20][C:19]([C:21]([O:23]C)=[O:22])=[CH:18][C:9]=3[NH:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].S(OC)(O[CH3:31])(=O)=O.[OH-].[Na+]>C1COCC1.CO>[CH:1]1([C:7]2[C:8]3[S:20][C:19]([C:21]([OH:23])=[O:22])=[CH:18][C:9]=3[N:10]([CH3:31])[C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 68467632methyl 6-cyclohexyl-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 111635876-Cyclohexyl-4-Methyl-5-Phenyl-4h-Thieno[3,2-B]pyrrole-2-Carboxylic AcidYield 42%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-a2697338598243f99310687f7fa44994
Source dataset
uspto-grants-2010_08
Patent number
US07781431B2

Reaction notes

Loading…