Pyrazole → 3-Ethyl 5-methyl 2-(trifluoromethyl)-6-(difluoromethyl)-4-(1-pyrazolyl)-3,5-pyridinedicarboxylate

HRID 2291507Notes

Reaction equation

HRID 2291507 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.C([Li])CCC.[F:11][CH:12]([F:33])[C:13]1[N:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[C:16]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:15](Cl)[C:14]=1[C:29]([O:31][CH3:32])=[O:30].[Li].N1C=CC=N1>O1CCCC1.O>[F:22][C:19]([F:20])([F:21])[C:17]1[C:16]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:15]([N:1]2[CH:5]=[CH:4][CH:3]=[N:2]2)[C:14]([C:29]([O:31][CH3:32])=[O:30])=[C:13]([CH:12]([F:11])[F:33])[N:18]=1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 140137713-Ethyl 5-methyl 6-(difluoromethyl)-4-chloro-2-(trifluoromethyl)-3,5-pyridinedicarboxylateHCID 70158464Pyrazole lithium saltHCID 178418339Butyllithium

Product 1

HCID 140138613-Ethyl 5-methyl 2-(trifluoromethyl)-6-(difluoromethyl)-4-(1-pyrazolyl)-3,5-pyridinedicarboxylateYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.94 g (0.014 mol) of pyrazole in 25 ml of anhydrous tetrahydrofuran was added 0.9 g (0.014 mol) of n-butyllithium. This cloudy solution was then transferred to a solution of 5 g (0.014 mol) of product of Example 103 in 25 ml of anhydrous THF. The solution turned red upon addition of the pyrazole lithium salt. After 45 minutes at room temperature the reaction was complete. The mixture was poured into 100 ml of water and extracted with two 75 ml portions of ether. The combined ether layers were washed with two 100 ml portions of water, dried (CaSO4), filtered and concentrated to 4.1 g of oil which was about 80% product. Trituration with petroleum ether gave 2.4 g (45%) of pure product; mp 42°-52° C. Recrystallization from cyclohexane afforded an analytical sample; mp 48.5°-50° C.

Workup

  1. extractionextracted with two 75 ml portions of ether
  2. washThe combined ether layers were washed with two 100 ml portions of water
  3. dry with materialdried (CaSO4)
  4. filtrationfiltered
  5. concentrationconcentrated to 4.1 g of oil which

Sources & evidence

ORD record
ord-3256256c57ac4b34bb582021c43cbcc4
Source dataset
uspto-grants-1989_01
Patent number
US04797149

Reaction notes

Loading…