Hydrochloric Acid → HCID 178448321, compound

HRID 550044Notes

Reaction equation

HRID 550044 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.C(O)C>[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 Acid2×HCID 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 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
2.5 °C

Procedure

Aqueous sodium hydroxide solution 2.0 M (approximately 100 ml; 200 mmol) is added to a stirred suspension of L-Valin (11.8 g; 100 mmol) and 2′-(1H-tetrazol-5-yl)-biphenyl-4-carbaldehyde (25.1 g; 100 mmol) in water (100 ml) at room temperature, until pH 11 is reached. The resulting clear solution is evaporated at 60° C. in vacuo, and remaining water is azeotro-pically removed with 1-butanol. The residue (imine as a solid foam) is dissolved in absolute ethanol (300 ml), and sodium borohydride (3.78 g; 100 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, it the reaction is complete (HPLC), quenched by addition of water (100 ml) and hydrochloric acid 2.0 M (80 ml; 160 mmol). The organic solvent (ethanol) 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 70 ml; 140 mmol) 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 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 azeotro-pically removed with 1-butanol
  3. dissolutionThe residue (imine as a solid foam) is dissolved in absolute ethanol (300 ml)
  4. concentrationThe remaining aqueous concentrate

Sources & evidence

ORD record
ord-3364f9218de24ed0b29ef15f163499cc
Source dataset
uspto-grants-2011_05
Patent number
US07943647B2

Reaction notes

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