1,2-Dibromoethane → Amitriptynol

HRID 1704772Notes

Reaction equation

HRID 1704772 reaction equation
[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5]Cl.[Mg].C(Br)CBr.[CH2:13]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14]1.[Cl-].[NH4+]>O1CCCC1>[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][C:21]1([OH:22])[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=2[CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:20]1=2

Participants

7

Reactant 5

HCID 78391,2-DibromoethaneHCID 14589DibenzosuberoneHCID 25517Ammonium ChlorideHCID 669603-Chloro-N,N-dimethyl-1-propanamineHCID 5462224Magnesium

Product 1

HCID 14390AmitriptynolYield 72.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

3-(Dimethylamino)propyl chloride (110 g) is dissolved in 600 ml of tetrahydrofuran. About 10% of this solution is added to the reaction flask containing 26.4 g of magnesium and 50 ml of tetrahydrofuran. The mixture is heated to reflux and reaction is initiated with ethylene dibromide. The remaining halide is added slowly (over about 30 minutes) to control the rate of reflux. The mixture is then heated under reflux for an additional 30 minutes. After cooling in an ice bath, 100 g of dibenzosuberone in 200 ml of tetrahydrofuran is added slowly (over about 30 minutes). The mixture is heated under reflux for 1.5 hours. After cooling in an ice bath, the mixture is decomposed by dropwise addition of saturated ammonium chloride solution (1 liter added in 2 hours). The mixture is stirred for an additional hour, the layers are separated and the aqueous layer is reextracted with ether. The combined organic layers are dried over magnesium sulfate, filtered and the solvent is removed in vacuo. The residue is dissolved in ether and extracted with 10% hydrochloric acid. The aqueous layer is basified with sodium hydroxide and extracted twice with ether. The ether extracts are dried, filtered, and the solvent is removed in vacuo leaving 103 g of a solid.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux
  3. customreaction
  4. temperatureof reflux
  5. temperatureThe mixture is then heated
  6. temperatureunder reflux for an additional 30 minutes
  7. temperatureAfter cooling in an ice bath
  8. temperatureThe mixture is heated
  9. temperatureunder reflux for 1.5 hours
  10. temperatureAfter cooling in an ice bath
  11. customthe layers are separated
  12. dry with materialThe combined organic layers are dried over magnesium sulfate
  13. filtrationfiltered
  14. customthe solvent is removed in vacuo
  15. dissolutionThe residue is dissolved in ether
  16. extractionextracted with 10% hydrochloric acid
  17. extractionextracted twice with ether
  18. dry with materialThe ether extracts are dried
  19. filtrationfiltered
  20. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-0e23de67406344d087a9032d9a90c774
Source dataset
uspto-grants-1978_11
Patent number
US04127717

Reaction notes

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