Isopropanol → Isopropyl 5-chloro-6-isopropoxynicotinate

HRID 1908757Notes

Reaction equation

HRID 1908757 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8](Cl)=[N:7][CH:6]=1)[CH3:2].[CH3:14][C:15]([O-:18])(C)[CH3:16].[K+].[CH:20](O)(C)C>C([O-])(O)=O.[Na+]>[CH:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([O:18][CH:15]([CH3:16])[CH3:14])=[N:7][CH:6]=1)([CH3:20])[CH3:2]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 16762519Ethyl 5,6-DichloronicotinateHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 22985641Isopropyl 5-chloro-6-isopropoxynicotinate

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

5,6-Dichloronicotinic acid ethyl ester (5.33 g, 24.2 mmol) is added to a solution of KOtBu (2.72 g, 24.2 mmol) in isopropanol (50 mL). The mixture is heated at 80° C. for 15 h before another portion of KOtBu (272 mg, 2.42 mmol) is added. Stirring is continued at 80° C. for 24 h. The mixture is diluted with sat. aq. NaHCO3 solution, extracted with diethyl ether, and the combined org. extracts are dried (Na2SO4), filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 5-chloro-6-isopropoxy-nicotinic acid isopropyl ester; LC-MS: tR=1.10 min, [M+1]+=258.05.

Workup

  1. additionis added
  2. extractionextracted with diethyl ether
  3. dry with materialextracts are dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by CC on silica gel eluting with heptane:EA 9:1

Sources & evidence

ORD record
ord-8dbf7f8cee264f2bb898b81731144729
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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