Method for preparation of citalopram
A general formula and compound technology, applied in the direction of organic chemical methods, chemical instruments and methods, medical preparations containing active ingredients, etc., can solve product impurity, difficult citalopram separation, and inconvenient industrial scale implementation, etc. problem, achieving the effect of reducing purification steps
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Examples
Embodiment 1
[0032] Embodiment 1 citalopram oxalate method 1
[0033] Zn(CN) 2 (1.2 g, 0.01 mol) and 1-(4′-fluorophenyl)-1-(3-dimethylaminopropyl)-5-bromophtalane (6.0 g, 0.016 mol) in DMF (40 ml ) was stirred at room temperature for 30 min under an atmosphere of argon. Dissolved oxygen was removed by bubbling argon through the reaction mixture for 10 minutes, then tetrakis(triphenylphosphine)palladium(0) (0.8 g, 0.0007 mol, 4.3 mol %) was added. The reaction mixture was then heated at 75 °C for 3 h, poured into water (200 mL) and extracted with ether (2 x 100 mL), dried (MgSO 4 ), filtered and concentrated under reduced pressure. The residue was dissolved in acetone (10 mL) and a solution of oxalic acid (0.145 g, 0.016 mol) in acetone (10 mL) was added with stirring. Citalopram oxalate was isolated by filtration, washed with cold ether and dried in vacuo to give purified citalopram, oxalate (6.1 g, 92%). Method 2
[0034] 1-(4′-fluorophenyl)-1-(3-dimethylaminopropyl)-5-bromophtalane...
Embodiment 2
[0035] Example 21-(4'-fluorophenyl)-1-(3-dimethylaminopropyl)-5-iodophtalane, oxalate
[0036] To a suspension of 5-iodo-2-benzo[c]furanone (phtalide) (26.0 g, 0.1 mol) in dry THF (100 mL) was added dropwise , 0.11 mol) and a solution of 4-fluorophenylmagnesium bromide in dry THF (100 mL) prepared from magnesium ingot (2.92 g, 0.12 mol). The temperature was kept below 0°C. After the addition was complete, the reaction mixture was stirred at 0 °C for 3 hours.
[0037] To the reaction mixture was added a second Grignard solution prepared from 3-dimethylaminopropyl chloride (14.6 g, 0.12 mol) and magnesium billet (3.2 g, 0.13 mol) in dry THF (100 mL). The temperature was kept below 0°C during the addition. After the addition was complete, the cooling was removed and the reaction mixture was stirred at room temperature for an additional 2 hours.
[0038] Then the reaction mixture was poured into ice water (200 ml) and NH 4 Cl saturated solution (100 ml) in the mixture. THF w...
Embodiment 3
[0041] Example 3 1-(3-Dimethylamino-1-propyl)-1-(4-fluorophenyl)-5-hydroxy-1,3-dihydroisobenzofuran, oxalate
[0042] To a suspension of 5-hydroxy-2-benzo[c]furanone (10.0 g, 0.07 mol) in dry THF (100 mL) was added dropwise the solution from 4-fluorobromobenzene at a temperature below 8°C. (24.0 g, 0.14 mol) and magnesium billet (4.38 g, 0.17 mol) in dry THF (80 mL) to prepare a solution of 4-fluorophenylmagnesium bromide. After the addition was complete, the reaction mixture was stirred overnight at room temperature.
[0043] To the reaction mixture was added 3-dimethylaminopropyl chloride (8.50 g, 0.07 mol) and magnesium turnip (1.93 g, 0.07 mol) in dry THF (40 mL) while keeping the temperature below 10°C. ) for the second Grignard solution prepared in . The reaction was stirred overnight.
[0044] The reaction mixture was poured into ice water (200 mL) and adjusted to pH 7 with aqueous ammonium chloride solution (300 mL), and finally separated into two phases. The aqueo...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More