Hydrochloric Acid → HCID 178448321, compound

HRID 550045Notes

Reaction equation

HRID 550045 reaction equation
[OH-].[Na+].[NH2:3][C@H:4]([C:8]([OH:10])=[O:9])[CH:5]([CH3:7])[CH3:6].[NH:11]1[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]2[CH:27]=[CH:26][C:25]([CH:28]=O)=[CH:24][CH:23]=2)=[N:14][N:13]=[N:12]1.[BH4-].[Na+].Cl>O.CO>[CH3:6][CH:5]([CH3:7])[C@H:4]([NH:3][CH2:28][C:25]1[CH:26]=[CH:27][C:22]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[C:15]2[NH:11][N:12]=[N:13][N:14]=2)=[CH:23][CH:24]=1)[C:8]([OH:10])=[O:9]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6287L-ValineHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 1785194042'-(1H-Tetrazol-5-yl)-1,1'-biphenyl-4-carboxaldehyde (Losartan Impurity)

Product 1

HCID 178448321HCID 178448321, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
2.5 °C

Procedure

Aqueous sodium hydroxide solution 10 M (approximately 41 ml; 410 mmol) is added to a stirred suspension of L-Valine (24.8 g; 210 mmol) and 2′-(1H-tetrazol-5-yl)-biphenyl-4-carbaldehyde (50 g; 200 mmol) in water (200 ml) at room temperature, until pH 11 is reached. The resulting clear solution is evaporated at 60° C. in vacuo, and remaining water is azeotropically removed with 1-butanol. The residue (imine as a solid foam) is dissolved in methanol (600 ml), and sodium borohydride (3.13 g; 80 mmol) is added in portions to the solution at 0-5° C. The reaction mixture is stirred for 30 min at 0-5° C., and, if the reaction is complete (HPLC), quenched by addition of water (300 ml) and hydrochloric acid 2.0 M (160 ml; 320 mmol). The organic solvent (methanol) is stripped off from the clear solution (pH 7) at 50° C. in vacuo. The remaining aqueous concentrate is adjusted to pH 2 by slow addition of hydrochloric acid 2.0 M (approximately 90 ml) at 40° C. During the addition the desired product precipitates. It is collected by filtration, washed with water and dried in vacuo. The crude product is suspended in methanol at 50° C., and stirred for a few minutes. Then the slurry is cooled to room temperature. (S)-3-methyl-2-((2′-(1H-tetrazol-5-yl)-biphenyl-4-yl-methyl)-amino)-butyric acid is collected by filtration and then dried in vacuo.

Workup

  1. customThe resulting clear solution is evaporated at 60° C. in vacuo
  2. customis azeotropically removed with 1-butanol
  3. dissolutionThe residue (imine as a solid foam) is dissolved in methanol (600 ml)
  4. concentrationThe remaining aqueous concentrate
  5. additionis adjusted to pH 2 by slow addition of hydrochloric acid 2.0 M (approximately 90 ml) at 40° C
  6. additionDuring the addition the desired product
  7. customprecipitates
  8. filtrationIt is collected by filtration
  9. washwashed with water
  10. customdried in vacuo
  11. customis suspended in methanol at 50° C.
  12. stirringstirred for a few minutes
  13. temperatureThen the slurry is cooled to room temperature
  14. filtration(S)-3-methyl-2-((2′-(1H-tetrazol-5-yl)-biphenyl-4-yl-methyl)-amino)-butyric acid is collected by filtration
  15. customdried in vacuo

Sources & evidence

ORD record
ord-ca9dcedf9365423fa9ad65ec56a53585
Source dataset
uspto-grants-2011_05
Patent number
US07943647B2

Reaction notes

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