Triethylamine → N-Methoxy-N-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

Temperatur

0 °C

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen, charged with 4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxylic acid (3.00 g, 16.5 mmol), methylene chloride (80 mL), and DMF (60 mg, 0.825 mmol) and cooled to 0° C. To the resulting solution, oxalyl chloride (2.31 g, 18.2 mmol) was added dropwise. After this addition was complete, the reaction was warmed to room temperature and stirred for 2 h. After this time, the reaction was concentrated to dryness under reduced pressure. The resulting white solid was dissolved in methylene chloride (80 mL) and the solution cooled to 0° C. Triethylamine (5.00 g, 49.5 mmol) and N,O-dimethylhydroxylamine (1.61 g, 16.5 mmol) were then added. After the addition was complete, the cooling bath was removed, and the reaction mixture was stirred at room temperature for 16 h. After this time, the reaction mixture was partitioned between water (100 mL) and ethyl acetate (200 mL). The layers were separated, and the aqueous phase was extracted with ethyl acetate (100 mL). The combined organic extracts were washed with water (100 mL), followed by brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration, and the solvent was evaporated under reduced pressure. The resulting residue was purified by flash chromatography to afford an 88% yield of 103a (3.29 g) as a white solid: mp 36-37° C.; 1H NMR (500 MHz, CDCl3) δ 7.79 (s, 1H), 3.76 (s, 3H), 3.34 (s, 3H), 2.78 (t, 2H, J=6.0 Hz), 2.62 (t, 2H, J=6.0 Hz), 1.82 (m, 4H); MS (APCI+) m/z 226.3 (M+H)

1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer
2. customwas purged with nitrogen
3. additionAfter this addition
4. temperaturethe reaction was warmed to room temperature
5. concentrationAfter this time, the reaction was concentrated to dryness under reduced pressure
6. dissolutionThe resulting white solid was dissolved in methylene chloride (80 mL)
7. temperaturethe solution cooled to 0° C
8. additionAfter the addition
9. customthe cooling bath was removed
10. stirringthe reaction mixture was stirred at room temperature for 16 h
11. customAfter this time, the reaction mixture was partitioned between water (100 mL) and ethyl acetate (200 mL)
12. customThe layers were separated
13. extractionthe aqueous phase was extracted with ethyl acetate (100 mL)
14. washThe combined organic extracts were washed with water (100 mL)
15. dry with materialdried over sodium sulfate
16. customThe drying agent was removed by filtration
17. customthe solvent was evaporated under reduced pressure
18. customThe resulting residue was purified by flash chromatography

ORD-Eintrag

ord-1cb16c0f67f3416f9df72bf30535603a

Quelldatensatz

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08722676B2