Tributylamine → ethyl alpha-acetyl-2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoate

HRID 1421629Notes

Reaction equation

HRID 1421629 reaction equation
[Cl:1][C:2]1[C:7](I)=[CH:6][C:5]([N:9]2[C:13](=[O:14])[N:12]([CH:15]([F:17])[F:16])[C:11]([CH3:18])=[N:10]2)=[C:4]([F:19])[CH:3]=1.[OH:20][CH:21]([CH3:29])[C:22](=[CH2:28])[C:23]([O:25][CH2:26][CH3:27])=[O:24].C(N(CCCC)CCCC)CCC.N1C=CN=N1>C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.C(OCC)C>[C:21]([CH:22]([CH2:28][C:7]1[CH:6]=[C:5]([N:9]2[C:13](=[O:14])[N:12]([CH:15]([F:17])[F:16])[C:11]([CH3:18])=[N:10]2)[C:4]([F:19])=[CH:3][C:2]=1[Cl:1])[C:23]([O:25][CH2:26][CH3:27])=[O:24])(=[O:20])[CH3:29]

Participants

7

Reactant 4

HCID 7622TributylamineHCID 10855587Butanoic acid, 3-hydroxy-2-methylene-, ethyl esterHCID 155100251-(4-chloro-2-fluoro-5-iodophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazoleHCID 178418936HCID 178418936, compound

Product 1

HCID 21255956ethyl alpha-acetyl-2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoateYield 103.7%

Reagents, catalysts & solvents 2

HCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
130 °C

Procedure

To a 50 mL roundbottom flask equipped with a mechanical stirrer and a thermometer were added 8.12 grams (0.02 mole--1.0 equiv.) of 1-(4-chloro-2-fluoro-5-iodophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole, 2.88 grams (0.02 mole--1.0 equiv.) of ethyl 3-hydroxy-2-methylenebutanoate, 7.4 grams (0.04 mole--2.0 equiv.) of tributylamine, and 0.077 gram (0.0002 mole--0.01 equiv.) of bis(benzonitrile)dichloropalladium(II). The reaction mixture was heated to 130° C., where it stirred for two hours. After this time TLC analysis of the reaction mixture indicated 100% conversion of the triazole starting material. To the reaction mixture was then added 50 mL of diethyl ether. The resulting mixture was washed with 6M sulfuric acid, water, and an aqueous saturated sodium chloride solution and then concentrated, yielding 8.7 grams of 75.5% pure ethyl α-acetyl-2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoate (84.9% yield). The 75.5% pure product was distilled at 200° C. and 0.01 mm of mercury, yielding 6.0 grams of 95.5% pure ethyl α-acetyl-2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoate.

Workup

  1. customTo a 50 mL roundbottom flask equipped with a mechanical stirrer
  2. washThe resulting mixture was washed with 6M sulfuric acid, water
  3. concentrationan aqueous saturated sodium chloride solution and then concentrated

Sources & evidence

ORD record
ord-3b10ad3b8818477f9dff4e5249fb046c
Source dataset
uspto-grants-2000_06
Patent number
US06077959

Reaction notes

Loading…