Toluene → HCID 12986614, compound

HRID 2065997Notes

Reaction equation

HRID 2065997 reaction equation
C1(C)C=CC=CC=1.[CH3:8][N:9]([CH2:11][CH2:12][CH2:13][C:14]1([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[O:22][CH2:21][C:20]2[CH:19]=[C:18]([C:23]#[N:24])[CH:17]=[CH:16][C:15]1=2)C.CC(Cl)OC(Cl)=O.C(N(C(C)C)CC)(C)C>CO>[CH3:8][NH:9][CH2:11][CH2:12][CH2:13][C@:14]1([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[O:22][CH2:21][C:20]2[CH:19]=[C:18]([C:23]#[N:24])[CH:17]=[CH:16][C:15]1=2

Participants

6

Reactant 4

HCID 1140TolueneHCID 2771CitalopramHCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformate

Product 1

HCID 12986614HCID 12986614, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
12.5 °C

Procedure

The toluene solution containing citalopram base was mixed with 1,2-dichloromethane (400 lit) and cooled to 10-15° C. A solution of 1-chloro ethyl chloroformate (110.8 Kg, 0.77 kmoles) was added to the reaction mass below 20° C. The reaction mass was further stirred for 30 minutes at 15-20° C. Diisopropylethyl amine (30.24 Kg, 0.23 kmoles) was added to the reaction mixture below 20° C. and further stirred for 30 minutes. The temperature of the reaction mass was raised to 60-65° C. and maintained for 2-3 hrs. The reaction mass was diluted with methanol (320 lit) at 60-65° C., heated further for 2-4 hrs at 60-65° C. and evaporated. The reaction mass was cooled to 25-30° C., diluted with water (480 lit) and stirred for 30 minutes. The phases were separated, aqueous layer was extracted with toluene (2×200 lit) and pH of the aqueous layer was adjusted to 9-10 with ammonia solution (320 lit). Toluene (400 lit) was added and the reaction mass stirred for 30 minutes. The organic layer was separated. Aqueous layer was extracted with toluene (2×200 lit). The combined toluene layer was washed with water, followed by brine. The toluene layer was dried on sodium sulphate, filtered and stirred with charcoal (15 Kg). The reaction mass was filtered and evaporated under reduced pressure to afford the title compound. Yield—140 Kg, 91.5%

Workup

  1. stirringfurther stirred for 30 minutes
  2. temperatureThe temperature of the reaction mass was raised to 60-65° C.
  3. temperaturemaintained for 2-3 hrs
  4. temperatureheated further for 2-4 hrs at 60-65° C.
  5. customevaporated
  6. temperatureThe reaction mass was cooled to 25-30° C.
  7. additiondiluted with water (480 lit)
  8. stirringstirred for 30 minutes
  9. customThe phases were separated
  10. extractionaqueous layer was extracted with toluene (2×200 lit)
  11. additionToluene (400 lit) was added
  12. stirringthe reaction mass stirred for 30 minutes
  13. customThe organic layer was separated
  14. extractionAqueous layer was extracted with toluene (2×200 lit)
  15. washThe combined toluene layer was washed with water
  16. dry with materialThe toluene layer was dried on sodium sulphate
  17. filtrationfiltered
  18. stirringstirred with charcoal (15 Kg)
  19. filtrationThe reaction mass was filtered
  20. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-e21aa0c64c0243458aa2d0aa342443cd
Source dataset
uspto-grants-2012_10
Patent number
US08288568B2

Reaction notes

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