Dimethylformamide → HCID 22049892, compound

HRID 602431Notes

Reaction equation

HRID 602431 reaction equation
[Br:1][C:2]1[C:3](=[O:21])[N:4]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][C:19]=2[CH3:20])[C:13]([O:15][CH3:16])=[O:14])[C:5]([CH3:9])=[CH:6][C:7]=1[OH:8].CN(C)C=O.C([O-])([O-])=O.[K+].[K+].[F:33][C:34]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:35]=1[CH2:36]Cl>O>[F:33][C:34]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:35]=1[CH2:36][O:8][C:7]1[CH:6]=[C:5]([CH3:9])[N:4]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][C:19]=2[CH3:20])[C:13]([O:15][CH3:16])=[O:14])[C:3](=[O:21])[C:2]=1[Br:1]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27369481-(Chloromethyl)-2,4-difluorobenzeneHCID 54746388HCID 54746388, compound

Product 1

HCID 22049892HCID 22049892, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

Methyl 3-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoate (4) (1.9 kg, 5.4 moles), N,N-dimethylformamide (4.8 L) and powdered K2CO3 (1.1 kg, 8.1 moles) were mixed together and heated to 55° C. under nitrogen. 2,4-difluorobenzyl chloride (964 g, 5.9 moles) was added at a rate such that the temperature was maintained below 65° C. After the addition, the mixture was heated at 65° C. for 3.5 hours. After 3 hours the reaction was complete and the reaction mixture was cooled to 20-25° C. with the addition of 19 L water. The solid was filtered and washed with 15 L water. The crude product was then purified by trituration in refluxing methanol (4 L). The mixture was cooled and the solid filtered to yield 2.32 kg (90%) product. 1H NMR (300 MHz, CDCl3) δ 1.90 (s, 3H), 2.11 (s, 3H), 3.87 (s, 3H), 5.25 (s, 2H), 6.11 (s, 1H), 6.88 (dt, J=4.8, 1.8 Hz, 1H), 6.96 (t, J=4.8 Hz, 1H), 7.42 (d, J=6 Hz, 1H), 7.59 (q, J=4.8 Hz, 1H), 7.74 (s, 1H), 8.02 (d, J=6 Hz, 1H). Anal. Cald. for C22H18BrF2NO4: C, 55.25; H, 3.79; N, 2.93. Found: C, 55.34; H, 3.83; N, 3.14.

Workup

  1. temperaturewas maintained below 65° C
  2. additionAfter the addition
  3. temperaturethe mixture was heated at 65° C. for 3.5 hours
  4. filtrationThe solid was filtered
  5. washwashed with 15 L water
  6. customThe crude product was then purified by trituration
  7. temperaturein refluxing methanol (4 L)
  8. temperatureThe mixture was cooled
  9. filtrationthe solid filtered

Sources & evidence

ORD record
ord-5f0007c4a031405898ea32a6e6bf17b5
Source dataset
uspto-grants-2011_03
Patent number
US07906536B2

Reaction notes

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