Hydrochloric Acid → HCID 67076762, compound

Temperature

-30 °C

(Benzhydrylidene-amino)-acetic acid ethyl ester (0.113 g, 0.414 mmol) was dissolved in DMF (3 ml) and cooled in an ice bath. Potassium tert-butoxide (94.8 mg, 0.828 mmol) was added, and the mixture was stirred for 10 min. The mixture was cooled to −30° C., and 3,4-bis-chloromethyl-thiophene (50 mg, 0.276 mmol) was added in one portion. The mixture was then placed into an ice bath again, and the reaction allowed to proceed for 20 min. The mixture was acidified with 2 N hydrochloric acid, stirred for 10 min and partitioned between water and diethyl ether. The aqueous phase was neutralized with a saturated sodium hydrogencarbonate solution and extracted with EA. The combined EA extracts were washed with a saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness. The residue was dissolved in diethyl ether, filtered, evaporated to dryness, acidified with hydrogen chloride in methanol and evaporated to dryness. The residue was stirred with an diethyl ether/HEP mixture, and the solid was filtered and dried in vacuo to give crude 5-amino-5,6-dihydro-4H-cyclopenta[c]thiophene-5-carboxylic acid ethyl ester hydrochloride. A part of the crude compound (27 mg, 0.109 mmol) was reacted without further purification with 4-methoxy-3-(2-m-tolyl-ethoxy)-benzoic acid in analogy to step 1 of example 15. After purification by preparative RP HPLC (water/ACN gradient), 23 mg of the title compound were obtained.

1. temperaturecooled in an ice bath
2. customThe mixture was then placed into an ice bath
3. waitto proceed for 20 min
4. stirringstirred for 10 min
5. custompartitioned between water and diethyl ether
6. extractionextracted with EA
7. washThe combined EA extracts were washed with a saturated sodium chloride solution
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. customevaporated to dryness
11. dissolutionThe residue was dissolved in diethyl ether
12. filtrationfiltered
13. customevaporated to dryness
14. customevaporated to dryness
15. stirringThe residue was stirred with an diethyl ether/HEP mixture
16. filtrationthe solid was filtered
17. customdried in vacuo

ORD record

ord-4ee9386d194b4ec7bd20e80c6a57d4e2

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802720B2