Acetic Acid → Methyl 6-chloro-2-methoxy-4-methylnicotinate

HRID 1517058Notes

Reaction equation

HRID 1517058 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([Cl:11])=[N:6][C:5]=1Cl.C[O-].[Na+].[C:17](O)(=[O:19])C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:13])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([Cl:11])=[N:6][C:5]=1[O:19][CH3:17]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 10942334Sodium MethoxideHCID 46911843Methyl 2,6-dichloro-4-methylnicotinate

Product 1

HCID 57441127Methyl 6-chloro-2-methoxy-4-methylnicotinateYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6.50 g (29.5 mmol) of 2,6-dichloro-4-methyl-nicotinic acid methyl ester in 75 ml of CH2Cl2 was added at 0° C. 6.56 ml (35.4 mmol) of a sodium methoxide solution (5.4 molar in MeOH). After 16 hours, the reaction mixture was warmed up to RT and stirred again 16 hours at this temperature and subsequently poured into crashed ice; then, the pH was adjusted to 4-5 with 2N acetic acid and the reaction mixture was extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (heptane/EtOAc 1.0 to 98:2) to give 5.79 g (91%) of the title compound as colorless solid. MS: 216.1 (MH+, 1Cl).

Workup

  1. additionsubsequently poured
  2. extractionthe reaction mixture was extracted twice with CH2Cl2
  3. washthe organic phases were washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromatography (heptane/EtOAc 1.0 to 98:2)

Sources & evidence

ORD record
ord-c53586a59b6b4120a2b741d661cdaf77
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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