Formaldehyde → Escitalopram Oxalate

HRID 1837317Notes

Reaction equation

HRID 1837317 reaction equation
[CH3:1][N:2]([CH2:4][CH2:5][CH2:6][C:7]1([C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)[O:15][CH2:14][C:13]2[CH:12]=[C:11]([C:16]#[N:17])[CH:10]=[CH:9][C:8]1=2)[CH3:3].CNCCC[C@]1(C2C=CC(F)=CC=2)OCC2C=C(C#N)C=CC1=2.C=O.O.O.[C:52]([OH:57])(=[O:56])[C:53]([OH:55])=[O:54]>C(O)C.C(O)=O>[CH3:1][N:2]([CH2:4][CH2:5][CH2:6][C@@:7]1([C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)[O:15][CH2:14][C:13]2[CH:12]=[C:11]([C:16]#[N:17])[CH:10]=[CH:9][C:8]1=2)[CH3:3].[C:53]([OH:55])([C:52]([OH:57])=[O:56])=[O:54]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 2771Citalopram2×HCID 61373Oxalic acid dihydrateHCID 12986614HCID 12986614, compound

Product 1

HCID 146571Escitalopram OxalateYield 79.3%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To the crude Citalopram (90 g, 0.28 mol) having desmethyl citalopram (7%, HPLC), formic acid (98%, 2.7 g) was added followed by aqueous formaldehyde (35%, 2.37 g). The reaction mass was heated at 85-95° C. for 30 min. HPLC indicated complete conversion of desmethyl impurity into Citalopram. The reaction mass was cooled to 30° C. and diluted with ethanol (900 ml). Oxalic acid dihydrate (41.94 g, 0.33 mol) was added and mass was heated to reflux. The obtained solution was cooled to 20-25° C. and stirring was continued for 2 hours at 20-25° C. The product thus obtained was filtered and crystallized from ethanol to provide highly pure 92 g of crystalline Citalopram oxalate having HPLC purity 99.7% and desmethyl citalopram impurity: Not Detected.

Workup

  1. additionwas added
  2. temperatureThe reaction mass was cooled to 30° C.
  3. temperaturemass was heated to reflux
  4. temperatureThe obtained solution was cooled to 20-25° C.
  5. customThe product thus obtained
  6. filtrationwas filtered
  7. customcrystallized from ethanol

Sources & evidence

ORD record
ord-edaaef0c570843d3b4150dc7176f65b4
Source dataset
uspto-grants-2004_08
Patent number
US06781003B1

Reaction notes

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