Sodium Cyanide → Citalopram

HRID 1384336Notes

Reaction equation

HRID 1384336 reaction equation
N[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.N([O-])=O.[Na+].C([O-])([O-])=O.[Na+].[Na+].[C:34]([Cu])#[N:35].[C-]#N.[Na+]>O.OS(O)(=O)=O.C1(C)C=CC=CC=1>[CH3:22][N:21]([CH3:23])[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)[C:8]2[C:4](=[CH:3][C:2]([C:34]#[N:35])=[CH:10][CH:9]=2)[CH2:5][O:6]1

Participants

9

Reactant 5

HCID 8929Sodium CyanideHCID 10340Sodium CarbonateHCID 109359335-Amino-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuranHCID 23668193Sodium NitriteHCID 178418546HCID 178418546, compound

Product 1

HCID 2771CitalopramYield 32%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 1118Sulfuric AcidSolventHCID 1140TolueneSolvent

Conditions

Temperature
2.5 °C

Procedure

5-Amino-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran (18 g, 0.06 mole) is dissolved in water (100 ml) and H2SO4(8 ml). NaNO2(4.1 g, 0.06 mole) is dissolved in water (20 ml) and added dropwise below 5° C. The diazotised solution is stirred for 0.5 hour at 0-5° C. pH is brought to 6.5 by adding a saturated solution of Na2CO3. This solution is added to a mixture of water (100 ml) and toluene (120 ml) containing CuCN(6 g, 0.067 mole) and NaCN (10 g, 0.2 mole) at 50-60C°. Stirring is continued for 0.5 hour. The phases are separated and the aqueous phase is further extracted with toluene (100 ml). The combined organic phase is washed with NaCN(10% aq., 2×50 ml). The solvent is removed in vacuo and the residue is chromatograhed on silica gel (ethyl acetate: n-heptane: triethylamine; 85:10:5 ) to give the title compound (6 g, 32%) as an oil.

Workup

  1. additionadded dropwise below 5° C
  2. stirringStirring
  3. waitis continued for 0.5 hour
  4. customThe phases are separated
  5. extractionthe aqueous phase is further extracted with toluene (100 ml)
  6. washThe combined organic phase is washed with NaCN(10% aq., 2×50 ml)
  7. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-7cc65714ed4547b1a3d15cfabd1c714c
Source dataset
uspto-grants-2001_07
Patent number
US06258842B1

Reaction notes

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