Hydrochloric Acid → Diethyl 2-(difluoromethyl)-4-ethyl-6-(trifluoromethyl)-3,5-pyridinedicarboxylate

HRID 847450Notes

Reaction equation

HRID 847450 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]1[NH:4][C:5]([C:21](F)([F:23])[F:22])=[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:7]([CH2:14][CH3:15])[C:8]=1[C:9]([O:11][CH2:12][CH3:13])=[O:10].N12CCCNC1C=CCCC2.Cl>O1CCCC1>[F:23][CH:21]([F:22])[C:5]1[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:7]([CH2:14][CH3:15])[C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:3]([C:2]([F:26])([F:1])[F:25])[N:4]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 139576211,4-Dihydro-2,6-bis(trifluoromethyl)-4-ethylpyridine-3,5-dicarboxylic acid diethyl esterHCID 150726561,2,3,4,6,7,8,10A-octahydropyrimido[1,2-a]azepine

Product 1

HCID 13957657Diethyl 2-(difluoromethyl)-4-ethyl-6-(trifluoromethyl)-3,5-pyridinedicarboxylateYield 78.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1558 g (4.00 moles) of diethyl 2,6-bis(trifluoromethyl)-1,4-dihydro-4-ethyl-3,5-pyridinedicarboxylate, 628 g (4.0 moles) of 1,8-diazabicyclo-[5.4.0]-undec-5-ene (DBU), and 500 ml of tetrahydrofuran is held at reflux for 19 hours, cooled and poured into a mixture of 2 kg of ice and 250 ml of concentrated hydrochloric acid. The organic layer is separated and the aqueous layer extracted with 500 ml of CH2Cl2 twice. The combined organic materials are dried (MgSO4) and concentrated. The residue is kugelrohr distilled at 1 torr (pot temperature of 150°-160° C.) to give 1158 g (78.5%) of desired product, nD25 1.4458.

Workup

  1. temperatureat reflux for 19 hours
  2. temperaturecooled
  3. customThe organic layer is separated
  4. extractionthe aqueous layer extracted with 500 ml of CH2Cl2 twice
  5. dry with materialThe combined organic materials are dried (MgSO4)
  6. concentrationconcentrated
  7. distillationThe residue is kugelrohr distilled at 1 torr (pot temperature of 150°-160° C.)

Sources & evidence

ORD record
ord-10f23d9c4c964db0a53c596e81f1cf66
Source dataset
uspto-grants-1992_08
Patent number
US05142055

Reaction notes

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