Sodium Methoxide → HCID 178447302, compound

HRID 12597Notes

Reaction equation

HRID 12597 reaction equation
Br[C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]([C:15](=[O:20])[CH2:16][CH2:17][CH2:18][CH3:19])[C@H:8]([C:12]([OH:14])=[O:13])[CH:9]([CH3:11])[CH3:10])=[CH:4][CH:3]=1.[NH:23]1[C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2B(O)O)=[N:26][N:25]=[N:24]1.C[O-].[Na+]>CO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:19][CH2:18][CH2:17][CH2:16][C:15]([N:7]([C@H:8]([C:12]([OH:14])=[O:13])[CH:9]([CH3:11])[CH3:10])[CH2:6][C:5]1[CH:4]=[CH:3][C:2]([C:33]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:27]2[NH:23][N:24]=[N:25][N:26]=2)=[CH:22][CH:21]=1)=[O:20]

Participants

7

Reactant 3

HCID 10942334Sodium MethoxideHCID 11696368N-[(4-Bromophenyl)methyl]-N-(1-oxopentyl)-L-valineHCID 178514830HCID 178514830, compound

Product 1

HCID 178447302HCID 178447302, compoundYield 58.1%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture made up of 1 g (2.70 mmol) of (4-bromobenzyl)-N-valeryl-L-valine, 0.513 g (2.70 mmol) of 2-(1H-tetrazol-5-yl)phenylboronic acid, 0.120 g of 5% Pd/C in paste (0.028 mmol of palladium) and 0.0084 g (0.032 mmol) of triphenylphosphine in a solution of 4.1 mL (21.5 mmol) of sodium methoxide in 30% methanol and 10 mL of methanol is heated at 70° C. for 10 h. The reaction is cooled to 20-25° C., the catalyst is filtered and the methanol distilled in vacuo. The resulting residue is dissolved in 25 mL of water and, following washing with 25 mL of AcOEt, is acidified to pH 3 with HCl 3N and extracted twice with 20 mL of AcOEt. The combined phases of AcOEt are dried with anhydrous Na2SO4 and following distillation of the solvent the crude product obtained is purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 15:5:0.2) to provide 0.683 g (58%) of Valsartan.

Workup

  1. temperatureThe reaction is cooled to 20-25° C.
  2. filtrationthe catalyst is filtered
  3. distillationthe methanol distilled in vacuo
  4. dissolutionThe resulting residue is dissolved in 25 mL of water
  5. washfollowing washing with 25 mL of AcOEt
  6. extractionextracted twice with 20 mL of AcOEt
  7. dry with materialThe combined phases of AcOEt are dried with anhydrous Na2SO4
  8. distillationdistillation of the solvent the crude product
  9. customobtained
  10. customis purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 15:5:0.2)

Sources & evidence

ORD record
ord-7b8ab9258581450a8bc951e07b1b819c
Source dataset
uspto-grants-2010_06
Patent number
US07728021B2

Reaction notes

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