Diethyl Ether → 2(S)-ethoxy-3-[4-(2-methyl-5-methylamino-2H-[1,2,4]triazol-3-yl)phenyl]propionic acid

HRID 910309Notes

Reaction equation

HRID 910309 reaction equation
S(OC)(O[CH3:5])(=O)=O.[NH2:8][C:9]1[N:10]=[C:11]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C@H:22]([O:27][CH2:28][CH3:29])[C:23]([O:25][CH3:26])=[O:24])=[CH:17][CH:16]=2)[N:12]([CH3:14])[N:13]=1.[CH2:30](OCC)C>C(N(CC)CC)C.O1CCCC1>[CH2:28]([O:27][C@@H:22]([CH2:21][C:18]1[CH:17]=[CH:16][C:15]([C:11]2[N:12]([CH3:14])[N:13]=[C:9]([NH:8][CH3:5])[N:10]=2)=[CH:20][CH:19]=1)[C:23]([O:25][CH3:26])=[O:24])[CH3:29].[CH2:28]([O:27][C@@H:22]([CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:11]2[N:12]([CH3:14])[N:13]=[C:9]([NH:8][CH3:30])[N:10]=2)=[CH:16][CH:17]=1)[C:23]([OH:25])=[O:24])[CH3:29]

Participants

7

Reactant 3

HCID 3283Diethyl EtherHCID 6497Dimethyl Sulfate2×HCID 67147868methyl 3-[4-(5-amino-2-methyl-2H-[1,2,4]triazol-3-yl)phenyl]-2(S)-ethoxypropanoate

Product 2

HCID 67147916methyl 2(S)-ethoxy-3-[4-(2-methyl-5-methylamino-2H-[1,2,4]triazol-3-yl)phenyl]propanoateYield 16%HCID 671481032(S)-ethoxy-3-[4-(2-methyl-5-methylamino-2H-[1,2,4]triazol-3-yl)phenyl]propionic acidYield 60%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
35 °C

Procedure

0.2 ml (2.2 mmol) of dimethyl sulfate is added to a mixture of 0.6 g (2 mmol) of methyl 3-[4-(5-amino-2-methyl-2H-[1,2,4]triazol-3-yl)phenyl]-2(S)-ethoxypropanoate, 0.3 ml (2.2 mmol) of triethylamine and 40 ml of ethyl ether. The reaction medium is heated at 35° C. for 4 hours. The reaction changed very little, 20 ml of tetrahydrofuran, 0.3 ml of triethylamine and 0.2 ml (2.2 mmol) of dimethyl sulfate are added and the reaction medium is heated at 40° C. for a further 24 hours. The reaction medium is evaporated to dryness. The residue obtained is purified by thin-layer chromatography on silica eluted with a 97/3 and then 95/5 dichloromethane/methanol mixture. 0.1 g (16%) of methyl 2(S)-ethoxy-3-[4-(2-methyl-5-methylamino-2H-[1,2,4]triazol-3-yl)phenyl]propanoate and 0.4 g (60%) of 2(S)-ethoxy-3-[4-(2-methyl-5-methylamino-2H-[1,2,4]triazol-3-yl)phenyl]propionic acid are obtained.

Workup

  1. temperaturethe reaction medium is heated at 40° C. for a further 24 hours
  2. customThe reaction medium is evaporated to dryness
  3. customThe residue obtained
  4. customis purified by thin-layer chromatography on silica
  5. washeluted with a 97/3

Sources & evidence

ORD record
ord-0a83640bd983458f9928ae145a2bb553
Source dataset
uspto-grants-2011_09
Patent number
US08022079B2

Reaction notes

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