Bromide ion → Citalopram

HRID 990289Notes

Reaction equation

HRID 990289 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]#[N:18])=[CH:14][CH:15]=3)[CH2:10][O:9]2)=[CH:4][CH:3]=1.[Br-].[CH3:20][N:21]([CH3:26])[CH2:22][CH2:23][CH2:24]Cl.[H-].[Na+]>CN(C)C=O.C1(C)C=CC=CC=1>[CH3:20][N:21]([CH3:26])[CH2:22][CH2:23][CH2:24][C:8]1([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:16]2[C:11](=[CH:12][C:13]([C:17]#[N:18])=[CH:14][CH:15]=2)[CH2:10][O:9]1

Participants

7

Reactant 4

HCID 259Bromide ionHCID 24758Sodium hydrideHCID 669603-Chloro-N,N-dimethyl-1-propanamineHCID 98561591-(4'-Fluorophenyl)-1,3-DihydroIsobenzofuran-5-Carbonitrile

Product 1

HCID 2771CitalopramYield 66.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
62.5 °C

Procedure

Under nitrogen atmosphere, to a solution of 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (3.0 g) in N,N-dimethylformamide (15 ml) were added tetra n-butfylammonium bromide (0.12 g) and N,N,N′,N′-tetramethylethylened amine (2.92 g). Thereto was added dropwise a solution of 3-(dimethyiamino)propyl chloride (2.0 g) in toluene (12 ml), and then a suspension of 60% sodium hydride (0.58 g) and liquid paraffin (1.5 ml) over 1.5 hr. The mixture was stirred at 61-64° C. for 7 hr. The reaction mixture was treated in the same manner as in Example 22 to give 1-(3-(dimethylamino)propyl)-1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram base) as a viscous oil (2.69 9, yield 66.1%). Hydrobromide thereof showed the same HPLC retention time and melting point as obtained in Example 22.

Workup

  1. additionThe reaction mixture was treated in the same manner as in Example 22

Sources & evidence

ORD record
ord-b7b47fc37e0040a5bcf9d004d89cc444
Source dataset
uspto-grants-2002_10
Patent number
US06458975B1

Reaction notes

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