Cysteamine → 2-(3-Methoxyphenyl)thiomorpholin-3-one

In a 500 mL round-bottomed flask, methyl 2-bromo-2-(3-methoxyphenyl)acetate (5.2 g, 20.1 mmol), 2-aminoethanethiol (1.55 g, 20.1 mmol) and potassium carbonate (5.55 g, 40.1 mmol) were combined with ethanol (150 ml) to give a light yellow suspension. The resultant mixture was stirred at 85° C. (bath temp.) for 2.5 h. No starting material remained. The intermediate, [2-amino-1-(3-methoxy-phenyl)-ethylsulfanyl]-acetic acid methyl ester, was the major product with 25% of the cyclized product. The mixture was further heated at reflux for an additional 4.5 h. Complete by LCMS. Reaction mixture was allowed to cool to room temperature and sit overnight. The reaction mixture was poured into 500 mL H2O and extracted with EtOAc (3×300 mL). The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The resulting pale yellow solid was triturated with cold ether and dried under vacuum to afford 2-(3-methoxyphenyl)thiomorpholin-3-one (3.7 g, 83%) as a yellow solid. (M+H)+=224 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.88 (td, J=5.81, 2.78 Hz, 2H) 3.67 (td, J=5.81, 3.54 Hz, 2H) 3.82 (s, 3H) 4.63 (s, 1H) 6.42 (br. s., 1H) 6.85 (ddd, J=8.34, 2.53, 0.76 Hz, 1H) 7.00 (t, J=2.15 Hz, 1H) 7.01-7.05 (m, 1H) 7.29 (t, J=7.93, 1H).

1. customto give a light yellow suspension
2. temperatureThe mixture was further heated
3. temperatureat reflux for an additional 4.5 h
4. customReaction mixture
5. extractionextracted with EtOAc (3×300 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe resulting pale yellow solid was triturated with cold ether
10. customdried under vacuum

ORD record

ord-f1e6777e58274b1a8f69b87725614e5b

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353096B2