Citalopram Hydrobromide → Desmethylcitalopram

Temperature

130 °C

The title compound was prepared according to the method of C. Jin, et al (Synthetic Communications, 2007, 37, 901-908). Thus, citalopram hydrobromide (5.5 g, 13.6 mmol) in 500 mL EtOAc was washed with dilute ammonium hydroxide (100 mL). The EtOAc layer was washed 3×100 mL saturated aqueous NaCl and dried with MgSO4. The solvent was removed in vacuo and the residue was treated with 1-chlorethyl chloroformate (29.6 mL, 27.2 mmol), heated to 130° C. for 6 hr, cooled to rt and concentrated in vacuo. The residue was dissolved with 150 mL CH3OH and heated for 5 hr at 65° C. The solvents were then removed in vacuo. The crude product was dissolved in THF (50 mL) and 50 mL of 1N NaOH were added. The mixture was stirred at rt for an additional 14 hr, then extracted with EtOAc (3×50 mL). The extracts were washed with saturated NaCl (3×100 mL), dried with Na2SO4 and the solvents removed. Chromatography on silica gel, eluting with a gradient (100% CH2Cl2 to 50% CH3OH: 50% CH2Cl2) gave the product as a clear oil, 3.102 g (74%).

1. washThe EtOAc layer was washed 3×100 mL saturated aqueous NaCl
2. dry with materialdried with MgSO4
3. customThe solvent was removed in vacuo
4. temperaturecooled to rt
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved with 150 mL CH3OH
7. temperatureheated for 5 hr at 65° C
8. customThe solvents were then removed in vacuo
9. dissolutionThe crude product was dissolved in THF (50 mL)
10. addition50 mL of 1N NaOH were added
11. extractionextracted with EtOAc (3×50 mL)
12. washThe extracts were washed with saturated NaCl (3×100 mL)
13. dry with materialdried with Na2SO4
14. customthe solvents removed
15. washChromatography on silica gel, eluting with a gradient (100% CH2Cl2 to 50% CH3OH: 50% CH2Cl2)

ORD record

ord-4d11c1f351214c2ab0d037c08e777647

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169237B1