Methanol → HCID 59321564, compound

HRID 2423490Notes

Reaction equation

HRID 2423490 reaction equation
[C:1]([CH2:6][C:7]([O:9][CH3:10])=[O:8])(=[O:5])[CH:2]([CH3:4])[CH3:3].C[O-].[Na+].CO.[Cl:16][C:17]1[C:22]([C:23](Cl)=[N:24]O)=[C:21]([Cl:27])[CH:20]=[CH:19][N:18]=1>C1COCC1>[Cl:16][C:17]1[C:22]([C:23]2[C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:1]([CH:2]([CH3:4])[CH3:3])[O:5][N:24]=2)=[C:21]([Cl:27])[CH:20]=[CH:19][N:18]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 2759969Methyl 4-methyl-3-oxopentanoateHCID 10942334Sodium MethoxideHCID 72255376HCID 72255376, compound

Product 1

HCID 59321564HCID 59321564, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl isobutyrylacetate (1.37 mL, 10.2 mmol) in THF (2.1 mL) was stirred at 0° C. as a 0.5 N solution of sodium methoxide in methanol (20.3 mL, 10.2 mmol) was added. A solution of 2,4-dichloro-N-hydroxy-3-pyridinecarboximidoyl chloride (1.94 g, 8.64 mmol) in THF (19 mL) was added and the resulting solution was allowed to warm to room temperature and stir overnight. The mixture was concentrated and the residue partitioned between ethyl acetate and brine. The organic layer was dried with MgSO4, filtered and concentrated. The residue was purified by chromatography (silica gel, hexanes to 3:7 ethyl acetate:hexanes gradient elution) and fractions containing the product concentrated. The residue was azetroped with methanol then dichloromethane to provide methyl 3-(2,4-dichloro-3-pyridinyl)-5-(1-methylethyl)-4-isoxazolecarboxylate (1.64 g, 66% as 0.15 dichloromethane). 1H NMR (400 MHz, DMSO-d6): δ 8.65 (d, J=5 Hz, 1H), 7.82 (d, J=5 Hz, 1H), 3.79 (septet, J=7 Hz, 1H), 3.63 (s, 3H), 1.34 (m, 6H).

Workup

  1. additionwas added
  2. concentrationThe mixture was concentrated
  3. customthe residue partitioned between ethyl acetate and brine
  4. dry with materialThe organic layer was dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (silica gel, hexanes to 3:7 ethyl acetate:hexanes gradient elution) and fractions
  8. additioncontaining the product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-dfe5f32c6d6142609cbc6cdbc9657034
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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