Ethylenediamine → Citalopram

HRID 1837316Notes

Reaction equation

HRID 1837316 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7]([CH2:18][CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[O:6][CH2:5]2.[CH3:24][N:25](C)C=O.C(N)CN>C1(C)C=CC=CC=1>[CH3:22][N:21]([CH2:20][CH2:19][CH2:18][C:7]1([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[O:6][CH2:5][C:4]2[CH:3]=[C:2]([C:24]#[N:25])[CH:10]=[CH:9][C:8]1=2)[CH3:23]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6228DimethylformamideHCID 101504575-BroModescyano CitalopraM

Product 1

HCID 2771Citalopram

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
145 °C

Procedure

Cuprous cyanide (85.4 g, 0.95 mol) was added to 5-bromo-1-(3-dimethylaminopropyl) 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran (200 g, 0.53 mol) and contents were heated to 140-150° C. After completion of reaction, N,N-dimethylformamide (200 ml) was added and reaction mass was further diluted with toluene (500 ml). The reaction mixture was cooled to 80° C. where aqueous ethylenediamine (50% w/v) was added and layers were separated. The organic layer was washed sequentially with aqueous EDTA (2% w/v) and water (2×200 ml). The organic layer was concentrated under reduced pressure to remove toluene. The residue was distilled in vacuum and crude Citalopram was obtained as oil. Yield: 110 g. The crude product contained 7% of desmethyl citalopram by HPLC.

Workup

  1. additionwas added
  2. customreaction mass
  3. additionwas added
  4. customlayers were separated
  5. washThe organic layer was washed sequentially with aqueous EDTA (2% w/v) and water (2×200 ml)
  6. concentrationThe organic layer was concentrated under reduced pressure
  7. customto remove toluene
  8. distillationThe residue was distilled in vacuum

Sources & evidence

ORD record
ord-78339f7eeb204fe78f804169ff02024a
Source dataset
uspto-grants-2004_08
Patent number
US06781003B1

Reaction notes

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