Ethyl Acetate → Levocetirizine dihydrochloride

HRID 554467Notes

Reaction equation

HRID 554467 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:9]2[CH2:14][CH2:13][N:12]([C:15](=O)[CH2:16][O:17][CH2:18][C:19]([OH:21])=[O:20])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:32])=O.C(OCC)(=O)C>O1CCCC1.O>[CH:26]1[CH:25]=[CH:24][C:23]([C@@H:8]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][O:17][CH2:18][C:19]([OH:21])=[O:20])[CH2:11][CH2:10]2)[C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:28][CH:27]=1.[ClH:32].[ClH:1]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 65578Oxalyl chlorideHCID 54193164HCID 54193164, compound

Product 1

HCID 9955977Levocetirizine dihydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

1 g of product of R-2-(2-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl-2-oxoethoxy)acetic acid was dissolved in 10 ml of dry tetrahydrofurane at 0° C. During intensive stirring 0.23 ml of oxalylchloride was added dropwise. After half an hour when the conversion of acid to acid chloride was completed 0.8 ml of dimethylsulphide borane complex (10 M calculated on BH3) was added in three portion. After the reaction was completed, the reaction mixture was poured in water (250 ml) and additionally stirred for half an hour. To the suspension 100 ml of ethyl acetate was added, pH was adjusted to 10 and the phases were separated. To the water phase 100 ml of methylene chloride was added, pH was adjusted with concentrated hydrochloric acid to 4.2 and phases were separated: the organic layer was rinsed with water, dried with sodium sulphate and evaporated to dryness. The oil residue was dissolved in 30 ml of acetone and HCl gas was introduced until pH reached the value of less than 1. The reaction mixture was heated to 60° C. and refluxed for 20 minutes. It was cooled to 30-35° C. and then filtered and the cake was washed with 20 ml of acetone. Then it was dried at 50-55° C. under reduced pressure (−0.08˜−0.1 MPa) for 8 hours. 720 mg of levocetirizine dihydrochloride were obtained.

Workup

  1. additionwas added dropwise
  2. addition0.8 ml of dimethylsulphide borane complex (10 M calculated on BH3) was added in three portion
  3. customthe phases were separated
  4. additionTo the water phase 100 ml of methylene chloride was added
  5. customwere separated
  6. washthe organic layer was rinsed with water
  7. dry with materialdried with sodium sulphate
  8. customevaporated to dryness
  9. dissolutionThe oil residue was dissolved in 30 ml of acetone
  10. additionHCl gas was introduced until pH
  11. temperaturerefluxed for 20 minutes
  12. temperatureIt was cooled to 30-35° C.
  13. filtrationfiltered
  14. washthe cake was washed with 20 ml of acetone
  15. customThen it was dried at 50-55° C. under reduced pressure (−0.08˜−0.1 MPa) for 8 hours

Sources & evidence

ORD record
ord-e4de837102534b88aa2f62677798e8c4
Source dataset
uspto-grants-2011_11
Patent number
US08049011B2

Reaction notes

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