p-Toluenesulfonic acid → HCID 18758665, compound

To a mixture of N-t-butoxycarbonylethanolamine (7.7 ml, 50 mmol) and 3,4-dihydropyran (5.7 ml, 62.5 mmol) in DCM (125 ml) was added 4-toluenesulphonic acid (100 mg, 0.5 mmol) and the mixture stirred at ambient temperature for 3 h. The solution was washed with saturated sodium hydrogen carbonate solution, dried and evaporated to dryness. The residue was filtered through a short pad of basic alumina with 10% EtOAc in hexane, the solvent evaporated to dryness, the residue dissolved in dimethylacetamide (5 ml) and added to a suspension of sodium hydride (400 mg of 50% dispersion in mineral oil, 10 mmol) in dimethylacetamide (5 ml). The mixture was heated at 50° C. for 1 h, cooled to ambient temperature and added to a solution of 1-fluoro-4-nitrobenzene (1.06 g, 7.5 mmol) in dimethylacetamide (5 ml) and heated at 50° C. for 4 h. The cooled mixture was poured onto water (150 ml), the aqueous solution was extracted with EtOAc, the EtOAc extracts were washed with brine, dried and evaporated. The residue was dissolved in ethanol (50 ml) and hydrogenated over 10% Pd/C for 4 h at ambient temperature. The catalyst was removed by filtration, the ethanol evaporated and the residue purified by column chromatography using 30% EtOAc in hexane to yield the title compound (640 mg, 1.9 mmol). NMR: 1.2-1.6 (m, 15H), 3.4-3.8 (m, 6H), 6.6 (d, 2H), 7.0 (d, 2H(; MS: 337 (M+H)+.

1. washThe solution was washed with saturated sodium hydrogen carbonate solution
2. customdried
3. customevaporated to dryness
4. filtrationThe residue was filtered through a short pad of basic alumina with 10% EtOAc in hexane
5. customthe solvent evaporated to dryness
6. dissolutionthe residue dissolved in dimethylacetamide (5 ml)
7. temperatureThe mixture was heated at 50° C. for 1 h
8. temperaturecooled to ambient temperature
9. temperatureheated at 50° C. for 4 h
10. additionThe cooled mixture was poured onto water (150 ml)
11. extractionthe aqueous solution was extracted with EtOAc
12. washthe EtOAc extracts were washed with brine
13. customdried
14. customevaporated
15. dissolutionThe residue was dissolved in ethanol (50 ml) and hydrogenated over 10% Pd/C for 4 h at ambient temperature
16. customThe catalyst was removed by filtration
17. customthe ethanol evaporated
18. customthe residue purified by column chromatography

ORD record

ord-c39e68b646044db19953418f988c2cb2

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06667342B1