N,N,N',N'-Tetramethylethylenediamine → 6-[2-(1-Aminoethyl)-4-methylphenyl]-4H-cyclopenta[b]-thiophene

温度

0 °C

A solution of compound of Example 23 (3.7 g, 9.9 mmol) and N,N,N',N'-tetramethylethylenediamine (0.75 mL, 5.0 mmol) in dry ether (70 ml) was cooled to 0° C. and treated with a solution of n-BuLi (2.5M) in hexane (8.0 mL, 20.0 mmol). The mixture was stirred at 0° C. for 0.25 hour and then at room temperature for an additional 3 hours. At this point the mixture was cooled to -78° C. A solution of 4,5-dihydro-6H-cyclopenta[b]thiophen-6-one (1.40 g, 10.1 mmol) in dry THF (15 ml) was then added dropwise and the resulting mixture was stirred at -78° to -60° C. over 1 hour. The reaction was quenched by addition of saturated NH4Cl solution and was allowed to warm to room temperature. The mixture was diluted with ether and H2O. The ether layer was separated and concentrated to leave an oil which was taken up in a mixture of 1N HCl (70 mL) and THF (105 mL). The resulting solution was stirred at room temperature overnight. Following removal of most of the THF in vacuo, the solution was extracted twice with ether. The extracts were set aside for later recovery of unreacted 4,5-dihydro-6H-cyclopenta[b]-thiophen-6-one while the aqueous layer was made basic by addition of solid NaOH and extracted twice again with ether. These extracts were combined, dried (Na2SO4) and concentrated in vacuo to leave an oil. This was placed under high vacuum and warmed to remove α,4-dimethyl-benzenemethanamine. Following flash chromatography on silica gel using EtOAc as eluant, the title compound was isolated as an oil (180 mg, 7%).

1. waitat room temperature for an additional 3 hours
2. temperatureAt this point the mixture was cooled to -78° C
3. stirringthe resulting mixture was stirred at -78° to -60° C. over 1 hour
4. customThe reaction was quenched by addition of saturated NH4Cl solution
5. temperatureto warm to room temperature
6. additionThe mixture was diluted with ether and H2O
7. customThe ether layer was separated
8. concentrationconcentrated
9. customto leave an oil which
10. stirringThe resulting solution was stirred at room temperature overnight
11. customremoval of most of the THF in vacuo
12. extractionthe solution was extracted twice with ether
13. additionwas made basic by addition of solid NaOH
14. extractionextracted twice again with ether
15. dry with materialdried (Na2SO4)
16. concentrationconcentrated in vacuo
17. customto leave an oil
18. temperaturewarmed
19. customto remove α,4-dimethyl-benzenemethanamine

ORDレコード

ord-bce034f87e1441df991573dc8fdc7d92

出典データセット

uspto-grants-1993_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05260309