Hydrochloric Acid → 4-(3-bromo-5-chlorophenoxy)-6-methylpyridin-2(1H)-one

HRID 1952346Notes

Reaction equation

HRID 1952346 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[CH:3]=1.[Br:10][C:11]1[CH:16]=[C:15](F)[CH:14]=[C:13]([Cl:18])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN1C(=O)CCC1.O>[Br:10][C:11]1[CH:16]=[C:15]([CH:14]=[C:13]([Cl:18])[CH:12]=1)[O:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27362231-Bromo-3-chloro-5-fluorobenzeneHCID 546914196-Methylpyridine-2,4-diol

Product 1

HCID 595297524-(3-bromo-5-chlorophenoxy)-6-methylpyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

4-Hydroxy-6-methylpyridin-2(1H)-one (3-2; 10.0 g; 80 mmol) and 1-bromo-3-chloro-5-fluorobenzene (16.74 g; 80 mmol) and potassium carbonate (33.1 g; 240 mmol) were suspended in NMP (200 mL) and then heated at 140° C. for 5 days. The reaction mixture was cooled to room temperature, diluted with water (900 mL) and the pH of the solution was adjusted to 5 with concentrated HCl. The solid was filtered off, washed with water and suctioned dry. The crude material was adsorbed onto silica and purified in 2 runs on a silica column eluted with DCM:MeOH to give the title product (9-1) as a yellow solid. Rf=0.6(DCM:MeOH, 95:5). LCMS: M+=315. 1H NMR (DMSO-d6): δ 11.48 (s, 1H), 7.65 (s, 1H), 7.43 (s, 1H), 7.36 (s,1H), 5.86 (s, 1H), 5.36 (s, 1H), 2.16 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe solid was filtered off
  3. washwashed with water
  4. customsuctioned dry
  5. custompurified in 2
  6. washeluted with DCM

Sources & evidence

ORD record
ord-3a3494070b96463684d2a7082af5a549
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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