Ethanol → 6-Chloro-5-methylnicotinic acid ethyl ester

HRID 1908774Notes

Reaction equation

HRID 1908774 reaction equation
[Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.OS(O)(=O)=O.[CH2:17](O)[CH3:18]>>[CH2:17]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([CH3:11])[C:2]([Cl:1])=[N:3][CH:4]=1)[CH3:18]

Participants

4

Reactant 3

HCID 702EthanolHCID 1118Sulfuric AcidHCID 123877296-Chloro-5-methylnicotinic acid

Product 1

HCID 574371976-Chloro-5-methylnicotinic acid ethyl ester

Procedure

A solution of 6-chloro-5-methyl-nicotinic acid (13.85 g, 80.75 mmol) in dry ethanol (200 mL) containing some drops of concentrated H2SO4 is stirred at reflux for 2 days. The solution is cooled to rt, the solvent evaporated, the residue dissolved in EA (200 mL) and washed with a solution of sat. aq. Na2CO3 (2×80 mL), 1M aq. KHSO4 (2×80 mL) and brine (50 mL). The org. phase is dried over MgSO4, filtered and evaporated to give 6-chloro-5-methyl-nicotinic acid ethyl ester (12.65 g) as a solid; LC-MS: tR=0.92 min; [M+1]+=200.10; 1H NMR (CDCl3) δ 1.43 (t, J=7.0 Hz, 3H), 2.46 (s, 3H), 4.43 (q, J=7.3 Hz, 2H), 8.16 (m, 1H), 8.84 (d, J=2.0 Hz, 1H).

Workup

  1. temperatureat reflux for 2 days
  2. customthe solvent evaporated
  3. dissolutionthe residue dissolved in EA (200 mL)
  4. washwashed with a solution of sat. aq. Na2CO3 (2×80 mL), 1M aq. KHSO4 (2×80 mL) and brine (50 mL)
  5. dry with materialphase is dried over MgSO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-d4c18e3959ae480a80b28d123d5da111
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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