Water → 3-Ethyl 5-methyl 6-(difluoromethyl)-4-(N-methylcyclopropylamino)-2-(trifluoromethyl)-3,5-pyridinedicarboxylate

HRID 2291504Notes

Reaction equation

HRID 2291504 reaction equation
[F:1][CH:2]([F:23])[C:3]1[N:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:5](Cl)[C:4]=1[C:19]([O:21][CH3:22])=[O:20].C(N(CC)CC)C.[CH3:31][NH:32][CH:33]1[CH2:35][CH2:34]1.O>CN(C=O)C>[F:1][CH:2]([F:23])[C:3]1[N:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:5]([N:32]([CH:33]2[CH2:35][CH2:34]2)[CH3:31])[C:4]=1[C:19]([O:21][CH3:22])=[O:20]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 11029756N-MethylcyclopropanamineHCID 140137713-Ethyl 5-methyl 6-(difluoromethyl)-4-chloro-2-(trifluoromethyl)-3,5-pyridinedicarboxylate

Product 1

HCID 140138563-Ethyl 5-methyl 6-(difluoromethyl)-4-(N-methylcyclopropylamino)-2-(trifluoromethyl)-3,5-pyridinedicarboxylateYield 50.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5.0 g (0.008 mol) of product from Example 103, 0.83 g (0.0082 mol) of triethylamine and 0.875 g (0.012 mol) of N-methylcyclopropylamine in 100 ml of DMF was stirred at room temperature for 12 hours. The reaction mixture was poured into H2O and extracted with diethyl ether. The ether phase was washed with H2O and dried (MgSO4). The dry ether phase was concentrated in vacuo to 2.4 g of a yellow oil. The crude product was purified by HPLC in 10% ethyl acetate/cyclohexane followed by kugelrohr distillation at 67 Pa and 125° C. pot temperature, affording 1.6 g (49%) of product as a yellow solid; mp 37°-40° C.

Workup

  1. extractionextracted with diethyl ether
  2. washThe ether phase was washed with H2O
  3. dry with materialdried (MgSO4)
  4. concentrationThe dry ether phase was concentrated in vacuo to 2.4 g of a yellow oil
  5. customThe crude product was purified by HPLC in 10% ethyl acetate/cyclohexane
  6. distillationfollowed by kugelrohr distillation at 67 Pa and 125° C. pot temperature

Sources & evidence

ORD record
ord-b8a66f518f904bfcad2bee3bd6712c65
Source dataset
uspto-grants-1989_01
Patent number
US04797149

Reaction notes

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