Ammonium Hydroxide → Citalopram

HRID 2230923

Reaction equation

HRID 2230923 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)([CH2:13][CH2:14][CH2:15][N:16]([CH3:18])[CH3:17])[O:8][CH2:7]2)(O)=O.S(N)([NH2:29])(=O)=O.S(Cl)(Cl)=O.[OH-].[NH4+]>S1(CCCC1)(=O)=O.CCCCCCC.O>[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)([CH2:13][CH2:14][CH2:15][N:16]([CH3:17])[CH3:18])[O:8][CH2:7]2)#[N:29]

Participants

8

Reactant 4

HCID 14923Ammonium HydroxideHCID 24386Thionyl ChlorideHCID 82267SulfamideHCID 99280441-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydro-5-Isobenzofurancarboxylic acid

Product 1

HCID 2771Citalopram

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8900HeptaneSolvent2×HCID 31347SulfolaneSolvent

Conditions

Temperature
130 °C

Procedure

5-Carboxy-1-(4-fluorophenyl)-1-(3-dimethylaminopropyl)-1,3-dihydro-isobenzofuran (5 g, 0.015 mole) and sulfamide (1.65 g, 0.017 mole) were dissolved in sulfolane (15 mL). Thionylchloride (2.25 g, 0.019 mole) was added at room temperature and the temperature of the reaction mixture was raised to 130° C. for 2 hours. The reaction mixture was allowed to cool to 75° C. and water (25 mL) was added. The temperature was held at 75° C. for 15 min, and then the reaction mixture was cooled to room temperature. pH was ajusted to 9 with ammonium hydroxide and then n-heptane (75 mL) was added. The temperature was raised to 70° C. and the hot n-heptane layer was isolated from which the title compound crystallised on cooling. Yield 3.77 g. Purity (HPLC peak area)>97%.

Workup

  1. temperatureto cool to 75° C.
  2. temperaturethe reaction mixture was cooled to room temperature
  3. temperatureThe temperature was raised to 70° C.

Sources & evidence

ORD record
ord-88300376b7be48dc9e3b2271621cbed7
Source dataset
uspto-grants-2002_07
Patent number
US06426422B1

Linked notes

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