3-Chloro-N,N-dimethyl-1-propanamine → Citalopram

HRID 853717Notes

Reaction equation

HRID 853717 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.[CH3:19][N:20]([CH2:22][CH2:23][CH2:24]Cl)[CH3:21]>>[CH3:19][N:20]([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)[O:9][CH2:10][C:11]2[CH:12]=[C:13]([C:17]#[N:18])[CH:14]=[CH:15][C:16]1=2)[CH3:21]

Participants

3

Reactant 2

HCID 669603-Chloro-N,N-dimethyl-1-propanamineHCID 98561591-(4'-Fluorophenyl)-1,3-DihydroIsobenzofuran-5-Carbonitrile

Product 1

HCID 2771Citalopram

Procedure

According to the present invention, the alkylation of 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (5-cyanophthalane) with N,N-dimethylaminopropylchloride may be carried out following prior art procedure, and preferably as described in U.S. Pat. No. 4,136,193. However, according to the process described in U.S. Pat. No. 4,136,193, after the completion of the alkylating reaction, the reaction mass is diluted with ice cold water and the aqueous layer is extracted into ether. The ether layer is then extracted with 20% aqueous acetic acid. The pH of the aqueous acidic layer is then adjusted to alkaline, e.g. pH 10-11, with sodium hydroxide and the citalopram base extracted into ether. The ether layer is then concentrated under reduced pressure to obtain citalopram base oil.

Workup

  1. custom4,136,193, after the completion of the alkylating reaction
  2. additionthe reaction mass is diluted with ice cold water
  3. extractionthe aqueous layer is extracted into ether
  4. extractionThe ether layer is then extracted with 20% aqueous acetic acid
  5. extractione.g. pH 10-11, with sodium hydroxide and the citalopram base extracted into ether
  6. concentrationThe ether layer is then concentrated under reduced pressure

Sources & evidence

ORD record
ord-32215a707e114a3689476b0602d4a2ef
Source dataset
uspto-grants-2007_08
Patent number
US07255741B2

Reaction notes

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