Sodium Acetate → 4'-hydroxymethyl-biphenyl-2-carbonitrile

HRID 875170Notes

Reaction equation

HRID 875170 reaction equation
CCCCC(N([C@H](C(O)=O)C(C)C)[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=2[C:21]2[NH:22]N=NN=2)=[CH:13][CH:14]=1)=O.BrCC1C=CC(C2C=CC=CC=2C#N)=CC=1.C([O-])(=[O:51])C.[Na+]>C(O)(=O)C>[C:21]([C:20]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:12]1[CH:11]=[CH:10][C:9]([CH2:8][OH:51])=[CH:14][CH:13]=1)#[N:22]

Participants

5

Reactant 3

HCID 517045Sodium AcetateHCID 15019124'-(Bromomethyl)-2-cyanobiphenylHCID 178447302HCID 178447302, compound

Product 1

HCID 13938964'-hydroxymethyl-biphenyl-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

According to U.S. Pat. No. 5,399,578, the process for the preparation of Valsartan (I) involves the reaction of 4′-bromomethyl-2-cyanobiphenyl (II) with sodium acetate and glacial acetic acid to produce 2′-cyano-4-hydroxymethylbiphenyl (III), which is reacted with oxalyl chloride in dichloromethane and dimethyl sulfoxide to produce 2′-cyano-4-formylbiphenyl (IV), which is further reacted with (L)-valine methyl ester hydrochloride (V) and sodium cyanoborohydride to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VI), followed by treatment with valeryl chloride to produce N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII), which is treated with tri-n-butyltin azide followed by flash chromatography to produce Valsartan of formula (I).

Sources & evidence

ORD record
ord-61fab70841e14736a16695e43af93b77
Source dataset
uspto-grants-2015_03
Patent number
US08981109B2

Reaction notes

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