Hydrochloric Acid → Dimethyl 6-(difluoromethyl)-4-(iso propylamino)-2-(trifluoromethyl)-3,5-pyridine-dicarboxylate

HRID 2291494Notes

Reaction equation

HRID 2291494 reaction equation
[F:1][CH:2]([F:26])[C:3]1[N:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[C:6]([C:13]([O:15][CH2:16]C)=[O:14])=[C:5]([NH:18][CH:19]([CH3:21])[CH3:20])[C:4]=1[C:22]([O:24][CH3:25])=[O:23].[OH-].[K+].Cl.C([O-])([O-])=O.[K+].[K+].CI>C(O)C.CN(C=O)C.O>[F:26][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:18][CH:19]([CH3:21])[CH3:20])[C:4]=1[C:22]([O:24][CH3:25])=[O:23]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 143734063-Ethyl 5-methyl 6-(difluoromethyl)-4-isopropylamino-2-(trifluoromethyl)-3,5-pyridinedicarboxylate

Product 1

HCID 14013774Dimethyl 6-(difluoromethyl)-4-(iso propylamino)-2-(trifluoromethyl)-3,5-pyridine-dicarboxylateYield 74.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

A mixture of 7.61 g (0.020 mol) of product of Example 63, 6.7 g (0.118 mol) of KOH and 30 ml of H2O in 200 ml of ethanol was refluxed for 16 hours. The reaction mixture was poured into 250 ml containing 50 ml of concentrated HCl, extracted with ether, dried (MgSO4) and concentrated in vacuo to a dark oil. This oil, 5.53 g (0.040 mol) of K2CO3 and 3.75 ml (0.060 mol) of methyl iodide in 50 ml of DMF was stirred at room temperature for 19 hours. The reaction mixture was poured into water, extracted with ether, dried (MgSO4) and concentrated in vacuo to 8.18 g of dark oil. This oil was chromatographed on the HPLC using 5% ethyl acetate/cyclohexane as eluting solvent affording 5.51 g (74.4%) of orange oil. A portion of this oil, 1.41 g, was kugelrohr distilled at 40 Pa, pot temperature 104° C., and 1.37 g of product was collected as a light yellow oil, n25D 1.4765.

Workup

  1. temperaturewas refluxed for 16 hours
  2. additionThe reaction mixture was poured into 250 ml
  3. extractionextracted with ether
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo to a dark oil
  6. extractionextracted with ether
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo to 8.18 g of dark oil
  9. customThis oil was chromatographed on the HPLC
  10. washas eluting solvent

Sources & evidence

ORD record
ord-f1c42e9d18c645ce80b9c7fafe10d516
Source dataset
uspto-grants-1989_01
Patent number
US04797149

Reaction notes

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