Hydrochloric Acid → 5-Ethyl 3-methyl 6-(difluoromethyl)-4-(isopropylamino)-2-(trifluoromethyl)-3,5-pyridinedicarboxylate

HRID 1649687Notes

Reaction equation

HRID 1649687 reaction equation
[F:1][CH:2]([F:25])[C:3]1[N:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[C:6]([C:13]([O:15][CH3:16])=[O:14])=[C:5]([NH:17][CH:18]([CH3:20])[CH3:19])[C:4]=1[C:21]([O:23][CH3:24])=[O:22].[OH-].[K+].Cl.[C:29]([O-])([O-])=O.[K+].[K+].C(I)C>CO.CN(C=O)C.O>[F:25][CH:2]([F:1])[C:3]1[N:8]=[C:7]([C:9]([F:12])([F:10])[F:11])[C:6]([C:13]([O:15][CH3:16])=[O:14])=[C:5]([NH:17][CH:18]([CH3:20])[CH3:19])[C:4]=1[C:21]([O:23][CH2:24][CH3:29])=[O:22]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 14013774Dimethyl 6-(difluoromethyl)-4-(iso propylamino)-2-(trifluoromethyl)-3,5-pyridine-dicarboxylate

Product 1

HCID 140138205-Ethyl 3-methyl 6-(difluoromethyl)-4-(isopropylamino)-2-(trifluoromethyl)-3,5-pyridinedicarboxylateYield 70.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent3×HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4.1 g (0.011 mol) of product of Example 76, 0.62 g (0.011 mol) of KOH and 5 ml of H2O in 50 ml of methanol was stirred at room temperature overnight. The reaction mixture was poured into 250 ml of H2O containing 50 ml of concentrated HCl, extracted with ether, dried (MgSO4) and concentrated in vacuo to 3.76 g of yellow oil. This oil, 1.52 g (0.011 mol) of K2CO3 and 0.88 ml (0.011 mol) of ethyl iodide in 30 ml of DMF was stirred at room temperature overnight. The reaction mixture was poured into water, extracted with ether, dried (MgSO4) and concentrated in vacuo to 3.64 g of yellow oil. Kugelrohr distillation at 53 Pa, pot temperature 103° C., afforded 2.98 g (70.5%) of product as a light yellow oil which solidified; mp 37°-39° C.

Workup

  1. extractionextracted with ether
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo to 3.76 g of yellow oil
  4. extractionextracted with ether
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo to 3.64 g of yellow oil
  7. distillationKugelrohr distillation at 53 Pa, pot temperature 103° C.

Sources & evidence

ORD record
ord-8148a8ccfeba4f8d8807de086dd8db70
Source dataset
uspto-grants-1990_05
Patent number
US04921530

Reaction notes

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