Hydrochloric Acid → 3-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid

HRID 602432Notes

Reaction equation

HRID 602432 reaction equation
[F:1][C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[C:10]([CH3:12])[N:9]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][C:22]=2[CH3:23])[C:16]([O:18]C)=[O:17])[C:8](=[O:24])[C:7]=1[Br:25].[OH-].[Na+].CC#N.Cl>O>[F:1][C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[C:10]([CH3:12])[N:9]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][C:22]=2[CH3:23])[C:16]([OH:18])=[O:17])[C:8](=[O:24])[C:7]=1[Br:25]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 22049892HCID 22049892, compound

Product 1

HCID 220504653-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acidYield 87.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 3-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoate (3) (3.4 kg, 7.1 moles), 2.5M NaOH (3.1 L. 7.8 moles), CH3CN (12 L) and 8.6 L water were mixed together and heated to 60° C., under nitrogen. Once the mixture became homogeneous the mixture was stirred for an additional hour. The reaction mixture was cooled to 20° C. and then treated with 865 ml concentrated HCl at a rate such that the temperature was maintained below 25° C. After the HCl addition was completed the mixture was stirred for another hour. The product was filtered and washed with 12 L CH3CN, dried to give 2.87 kg (87%) adduct. 1H NMR (300 MHz, CD3OD) δ 7.87 (dd, J=7.8, 1.6 Hz, 1H), 7.82 (d, J=1.8 Hz, 1H), 7.69 (q, J=8.1 Hz, 1H), 7.57 (d, J=8.1 Hz, 1H), 7.09 (dt, J=2.2, 8.6 Hz, 1H), 6.7 (s, 1H), 5.4 (s, 2H), 2.14 (s, 3H), 2.02 (s, 3H) (d, J=2.4 Hz, 1H), 3.94 (s, 3H), 2.15 (s, 3H), 1.91 (s, 3H). ES-HRMS m/z 464.0275 (M+H calcd for C21H17BrF2NO4 requires 464.0304). Anal. Cald. for C21H16BrF2NO4: C, 54.33; H, 3.47; N, 3.02. Found: C, 54.40; H, 3.42; N, 3.17

Workup

  1. temperatureThe reaction mixture was cooled to 20° C.
  2. temperaturewas maintained below 25° C
  3. stirringwas stirred for another hour
  4. filtrationThe product was filtered
  5. washwashed with 12 L CH3CN
  6. customdried

Sources & evidence

ORD record
ord-8fe183a1da4a466d961242edb8205206
Source dataset
uspto-grants-2011_03
Patent number
US07906536B2

Reaction notes

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