Ammonium formate → HCID 178447302, compound

HRID 2116617Notes

Reaction equation

HRID 2116617 reaction equation
[CH:1]([CH:4]1[C:8](=[O:9])[O:7][CH:6]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[N:26](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:25]=[N:24][N:23]=3)=[CH:12][CH:11]=2)[N:5]1[C:46](=[O:51])[CH2:47][CH2:48][CH2:49][CH3:50])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>CN(C)C(=O)C.[Pd]>[CH3:50][CH2:49][CH2:48][CH2:47][C:46]([N:5]([C@H:4]([C:8]([OH:9])=[O:7])[CH:1]([CH3:3])[CH3:2])[CH2:6][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]2[NH:23][N:24]=[N:25][N:26]=2)=[CH:14][CH:15]=1)=[O:51]

Participants

5

Reactant 2

HCID 2723923Ammonium formate2×HCID 23073590HCID 23073590, compound

Product 1

HCID 178447302HCID 178447302, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

1.0 g (1.5 mmoles) of 4-isopropyl-3-pentanoyl-2-[2′-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-yl]oxazolidin-5-one are reacted in 50 ml of N,N,-dimethyl-acetamide with 1.2 g of ammonium formate (19.0 mmoles) and 1.2 g of 5% Pd/C catalyst. The temperature is raised to 90° C. and ammonium formate is added in 1.2 g (19.0 mmoles) portions, at 2 hours interval, until disappearance of the starting substrate. The mixture is cooled and the catalyst is filtered off. tert-Butyl methyl ether and 20% sulfuric acid are added to about pH 2, then sodium chloride to saturation of the aqueous phase. The organic phase is separated and washed with water 3 times. The organic phase is alkalinised with a 10% sodium hydroxide solution. The aqueous phase containing the salified product is separated and washed with tert-butyl methyl ether. Ethyl acetate is added and acidified with a 5% hydrochloric acid solution. The organic phase is separated, dried over sodium sulfate, filtered and concentrated under reduced pressure to a residue. Crystallization from isopropyl ether affords 0.44 g of valsartan (1.05 mmoles; yield: 70%), having purity higher than 99.5% and content in azide derivatives lower than 20 ppm.

Workup

  1. temperatureThe mixture is cooled
  2. filtrationthe catalyst is filtered off
  3. additiontert-Butyl methyl ether and 20% sulfuric acid are added to about pH 2
  4. customThe organic phase is separated
  5. washwashed with water 3 times
  6. additionThe aqueous phase containing the salified product
  7. customis separated
  8. washwashed with tert-butyl methyl ether
  9. additionEthyl acetate is added
  10. customThe organic phase is separated
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure to a residue
  14. customCrystallization from isopropyl ether

Sources & evidence

ORD record
ord-ca8f078dac814870b31638fce7678222
Source dataset
uspto-grants-2008_10
Patent number
US07439261B2

Reaction notes

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