Hydrochloric Acid → Losartan

HRID 1824567Notes

Reaction equation

HRID 1824567 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:22]([C:23]4[N:27]=[N:26][N:25](C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[N:24]=4)=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:13][CH:12]=2)[C:8]([CH2:47][OH:48])=[C:7]([Cl:49])[N:6]=1.Cl.[OH-].[Na+]>CO>[CH3:1][CH2:2][CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=3[C:23]3[N:27]=[N:26][NH:25][N:24]=3)=[CH:13][CH:12]=2)[C:8]([CH2:47][OH:48])=[C:7]([Cl:49])[N:6]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 10865273Trityllosartan

Product 1

HCID 3961LosartanYield 88.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
10 °C

Procedure

In the last step, trityl losartan was suspended in methanol and cooled to ˜10° C. 3.4 N Hydrochloric acid was added to the slurry. After a period of time, the pH of the reaction mixture was raised to 13 with 10 N NaOH. Methanol was then distilled off while makeup water was added. After distillation, additional water and toluene were added. The toluene phase was separated and the aqueous phase was extracted once more with toluene. Ethyl acetate and acetic acid were then added to the aqueous phase. Losartan was recovered from the aqueous phase as a solid and further purified by slurrying in ethyl acetate. Losartan was obtained in 88.5% yield and 98.8% purity as determined by HPLC. This process is also described in U.S. Pat. Nos. 5,128,355 and 5,155,188.

Workup

  1. waitAfter a period of time
  2. distillationMethanol was then distilled off while makeup water
  3. additionwas added
  4. distillationAfter distillation, additional water and toluene
  5. additionwere added
  6. customThe toluene phase was separated
  7. extractionthe aqueous phase was extracted once more with toluene
  8. additionEthyl acetate and acetic acid were then added to the aqueous phase
  9. customLosartan was recovered from the aqueous phase as a solid
  10. customfurther purified

Sources & evidence

ORD record
ord-9b8a29f1537c4e028c1daadc33b0af9d
Source dataset
uspto-grants-2006_05
Patent number
US07041832B2

Reaction notes

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