Water → methyl 3-(4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoate

HRID 1867072Notes

Reaction equation

HRID 1867072 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[O:5][C:4](=O)[CH:3]=1.[CH3:10][O:11][C:12](=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([NH2:19])[C:14]=1C.O.Cl[C:24]1C=CC=CC=1Cl>>[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:19]([C:15]2[CH:14]=[C:13]([CH:18]=[CH:17][C:16]=2[CH3:24])[C:12]([O:11][CH3:10])=[O:21])[C:4](=[O:5])[CH:3]=1

Participants

5

Reactant 4

HCID 962WaterHCID 72391,2-DichlorobenzeneHCID 38010253-Amino-2-methylbenzoic acid methyl esterHCID 546757574-Hydroxy-6-methyl-2-pyrone

Product 1

HCID 54724193methyl 3-(4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoateYield 40%

Conditions

Temperature
110 °C

Procedure

4-Hydroxy-6-methyl-2-pyrone (22.9 g, 181.6 mmol) and methyl-3-amino-2-methylbenzoate (25 g, 151.3 mmol) were suspended in 50 ml of 1,2-dichlorobenzene in a 250 ml, 3-necked round bottom flask equipped with a J-Kem temperature controller probe, a Dean-Stark trap, and a heating mantle. The reaction was heated to 165° C. for 15 minutes, during which, water and some 1,2-dichlorobenzene was collected in the Dean Stark trap. The reaction was allowed to cool to about 110° C. At this point, 200 ml of toluene was added. The flask was plunged into a 0° C. ice bath while stirring. “Oiling out” occurred. Perhaps too much toluene was added so some of the solvent was removed in vacuo. The oil went back into solution and a light brown precipitate remained. The toluene mixture was allowed to stir for 72 hours at room temperature. A precipitate was collected on a filter pad. The precipitate was filtered and washed 3 Limes with toluene, 3 times with 50° C. water to remove excess pyrone, and dried in vacuo to give a tan solid (16.5 g, 40% yield). 1H NMR (300 MHz, CD3OD) δ 8.06 (dd, J=8.06, 1.61 Hz, 1H), 7.80 (d, J=1.61 Hz, 1H), 7.56 (d, J=3.06, Hz, 1H), 6.15 (dd, J=2.42, 0.81 Hz, 1H), 5.86 (d, J=2.42 1H), 3.94 (s, 3H), 2.15 (s, 3H), 1.91 (s, 3H); ES-MS m/z 274 (M+H). ES-HRMS m/z 274.1066 (M+H calcd for C15H16NO4 requires 274.1074).

Workup

  1. customequipped with a J-Kem temperature controller probe
  2. customsome 1,2-dichlorobenzene was collected in the Dean Stark trap
  3. additionAt this point, 200 ml of toluene was added
  4. customwas plunged into a 0° C.
  5. additionPerhaps too much toluene was added so some of the solvent
  6. customwas removed in vacuo
  7. stirringto stir for 72 hours at room temperature
  8. customA precipitate was collected on a filter pad
  9. filtrationThe precipitate was filtered
  10. washwashed 3 Limes with toluene, 3 times with 50° C. water
  11. customto remove excess pyrone
  12. customdried in vacuo

Sources & evidence

ORD record
ord-c1044465cf13478da8298e34b454952b
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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