Losartan → Losartan potassium salt

HRID 917007

Reaction equation

HRID 917007 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][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:15][CH:16]=2)[C:8]([CH2:28][OH:29])=[C:7]([Cl:30])[N:6]=1.[OH-].[K+:32]>C(O)(C)C.O.CCCCCCC>[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][N-:25][N:24]=3)=[CH:13][CH:12]=2)[C:8]([CH2:28][OH:29])=[C:7]([Cl:30])[N:6]=1.[K+:32]

Participants

6

Reactant 2

HCID 3961LosartanHCID 14797Potassium Hydroxide

Product 1

HCID 11476710Losartan potassium saltYield 77.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8900HeptaneSolvent

Procedure

As already described, to 10.2 g crude losartan of Example 14 (chromatographic purity 98.73%) in 59 ml i-propanol, a solution of 1.4 g potassium hydroxide in 1.5 ml water at a temperature of 38-40° C. to a pH of 10 over half an hour was added. Approximately 19 ml of azeotropic mixture i-propanol/water were removed by distillation, 36 ml n-heptane were added, and reaction mixture was stirred at room temperature until a white solid was formed. The resulting mixture was diluted with 14 ml n-heptane, filtered, washed with 26 ml n-heptane, and dried in vacuo at 50° C. to yield 8.57 g losartan potassium (yield: 77%, chromatographic purity: 99.67%).

Workup

  1. customApproximately 19 ml of azeotropic mixture i-propanol/water were removed by distillation, 36 ml n-heptane
  2. additionwere added
  3. customreaction mixture
  4. customwas formed
  5. filtrationfiltered
  6. washwashed with 26 ml n-heptane
  7. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-90f75912b30741d4915d400fd59d5da6
Source dataset
uspto-grants-2007_09
Patent number
US07271269B2

Linked notes

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