Benzoyl Peroxide → HCID 70293409, compound

To a solution of ethyl 2-methyl-6-phenylnicotinate (prepared according to Spath et al. [Monatsh. Chem. (1928) 49:265]) (1.00 g, 4.10 mmol) in carbon tetrachloride (10 mL) was added N-bromosuccinimide (0.81 g, 4.60 mmol) and benzoyl peroxide (0.05g). The reaction was heated at reflux for 18 h, cooled and filtered. The filtrate was concentrated and redissolved in anhydrous tetrahydofuran (10 mL). Methyl thioglycolate (0.37 mL, 4.10 mmol) was added, followed by sodium hydride (80%, 0.12 g, 4.1 mmol). The reaction mixture was allowed to stir at room temperature for 3 h. Additional sodium hydride (80%, 0.14 g, 4.6 mmol) was added and the solution was heated to gentle reflux for 18 h. The reaction was cooled to 0° C. and quenched with water (20 mL). The mixture was washed with ethyl acetate (50 mL). The aqueous layer was acidified to pH 5 with acetic acid and the product extracted with ethyl acetate (3×40 mL). The organic extract was washed with brine (10 mL), dried and evaporated to provide an orange oil. Chromatography on silica gel using 6:1 hexane:ethyl acetate as eluant afforded a mixture of uncyclised compound as a yellow oil (20%) and the desired methyl 7-phenyl-8-aza-isothiochroman-4-one-3-carboxylate (23%) as a yellow solid, mp 78°-81° C. This material was heated at reflux in 3N aqueous hydrochloric acid (30 mL) for 12 h, then cooled and made basic. Extraction with ethyl acetate (4×50 mL) afforded a semi-solid mass after drying and evaporation. Chromatography on silica gel using 7:1 hexane/ethyl acetate as eluant afforded 7-phenyl-8-aza-isothiochroman-4-one as a yellow solid (68%), mp 97°-99° C.; 1H NMR (CDCl3) δ 3.58 (s, 2H), 4.14 (s, 2H), 7.48 (m, 4H), 7.78 (d, 1H), 8.04-8.07 (m, 2H), 8.40 (d, 1H); IR (KBr) 1680 cm-1 ; Mass spectrum m/z 242 (M+H); Anal. calcd. for C14H11NOS: C 69.68 H 4.54 N 5.80; Found C 69.39 H 4.58 N 5.69.

1. temperatureThe reaction was heated
2. temperatureat reflux for 18 h
3. temperaturecooled
4. filtrationfiltered
5. concentrationThe filtrate was concentrated
6. dissolutionredissolved in anhydrous tetrahydofuran (10 mL)
7. temperaturethe solution was heated
8. temperatureto gentle reflux for 18 h
9. temperatureThe reaction was cooled to 0° C.
10. customquenched with water (20 mL)
11. washThe mixture was washed with ethyl acetate (50 mL)
12. extractionthe product extracted with ethyl acetate (3×40 mL)
13. extractionThe organic extract
14. washwas washed with brine (10 mL)
15. customdried
16. customevaporated
17. customto provide an orange oil
18. temperatureThis material was heated
19. temperaturecooled
20. extractionExtraction with ethyl acetate (4×50 mL)
21. customafforded a semi-solid mass
22. customafter drying
23. customevaporation

ORD record

ord-5a2bbfebc991471b921a2de29a2e4f26

Source dataset

uspto-grants-1997_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05639759