Dimethylformamide → Methyl 3-(4-cyclopropyl-2-(methoxymethyl)oxazol-5-yl)-4-methylbenzoate

HRID 1487832Notes

Reaction equation

HRID 1487832 reaction equation
Br[CH:2]([CH:16]1[CH2:18][CH2:17]1)[C:3]([C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][C:14]=1[CH3:15])[C:8]([O:10][CH3:11])=[O:9])=[O:4].Cl.[CH3:20][O:21][CH2:22][C:23](=[NH:25])[NH2:24].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C(OCC)(=O)C>[CH:16]1([C:2]2[N:24]=[C:23]([CH2:22][O:21][CH3:20])[NH:25][C:3]=2[C:5]2[CH:6]=[C:7]([CH:12]=[CH:13][C:14]=2[CH3:15])[C:8]([O:10][CH3:11])=[O:9])[CH2:18][CH2:17]1.[CH:16]1([C:2]2[N:24]=[C:23]([CH2:22][O:21][CH3:20])[O:4][C:3]=2[C:5]2[CH:6]=[C:7]([CH:12]=[CH:13][C:14]=2[CH3:15])[C:8]([O:10][CH3:11])=[O:9])[CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 135486022-Methoxyethanimidamide hydrochloride2×HCID 90021300HCID 90021300, compound2×

Product 2

HCID 90021498Methyl 3-(4-cyclopropyl-2-(methoxymethyl)oxazol-5-yl)-4-methylbenzoateYield 41%HCID 178494661HCID 178494661, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Into a 100-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed methyl 3-(2-bromo-2-cyclopropylacetyl)-4-methylbenzoate (compound 4.6, 150 mg, 0.48 mmol), 2-methoxyacetimidamide hydrochloride (compound 4.7, 90 mg, 0.72 mmol), potassium carbonate (200 mg, 1.44 mmol), and N,N-dimethylformamide (15 mL). The resulting mixture was stirred at 80° C. for 3 h, then diluted with ethyl acetate (100 mL). The mixture was washed with brine (3×30 mL) and water (3×30 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:2) as the eluent to yield methyl 3-(4-cyclopropyl-2-(methoxymethyl)-1H-imidazol-5-yl)-4-methylbenzoate (compound 4.8) (30 mg, 21%) and methyl 3-(4-cyclopropyl-2-(methoxymethyl)oxazol-5-yl)-4-methylbenzoate (compound 4.9) (60 mg, 41%), both as a yellow oils.

Workup

  1. customInto a 100-mL round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. washThe mixture was washed with brine (3×30 mL) and water (3×30 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:2) as the eluent

Sources & evidence

ORD record
ord-7dc9047c0b734d5aafec367775601e2a
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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