Potassium Phosphate, Tribasic → HCID 136160552, compound

HRID 1930188Notes

Reaction equation

HRID 1930188 reaction equation
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[OH:17].Cl[C:19]1[N:24]=[C:23]([C:25]([NH2:27])=[O:26])[C:22]([CH3:28])=[N:21][C:20]=1[CH3:29].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C(O)C.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[F:1][C:2]1[CH:7]=[C:6]([C:19]2[N:24]=[C:23]([C:25]([NH2:27])=[O:26])[C:22]([CH3:28])=[N:21][C:20]=2[CH3:29])[CH:5]=[CH:4][C:3]=1[OH:17]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 115722382-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol2×HCID 57992034HCID 57992034, compound

Product 1

HCID 136160552HCID 136160552, compound

Reagents, catalysts & solvents 4

HCID 53485975CID 53485975CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (Intermediate 31-4; 348 g, 1169 mmol) (80% strength by proton NMR), 6-chloro-3,5-dimethylpyrazine-2-carboxamide (217 g, 1169 mmol) and potassium phosphate tribasic (298 g, 1403 mmol) in DME (3.6 L), ethanol (0.9 L) and water (1.8 L) was stirred. The mixture was degassed with nitrogen for 30 minutes at 30° C. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (8.60 g, 10.5 mmol) was then added to the suspension. The reaction was further degassed for 10 minutes before being heated to 80° C., stirred for 4 hours. The reaction was cooled to 25° C. The solvents were then removed in vacuo until a slurry in water remained. A solution of citric acid (640 g) in water (6.0 L) was then added slowly with stirring. The suspension was filtered, washed with water (2×2.5 L), MTBE (2.5 L), sucked dry on the sinter and then dried at 65° C. in a vacuum over for 48 hours. Gave 6-(3-fluoro-4-hydroxyphenyl)-3,5-dimethylpyrazine-2-carboxamide (295 g, 97%) as a light brown solid.

Workup

  1. customThe mixture was degassed with nitrogen for 30 minutes at 30° C
  2. customThe reaction was further degassed for 10 minutes
  3. stirringstirred for 4 hours
  4. temperatureThe reaction was cooled to 25° C
  5. customThe solvents were then removed in vacuo until a slurry in water
  6. additionA solution of citric acid (640 g) in water (6.0 L) was then added slowly
  7. stirringwith stirring
  8. filtrationThe suspension was filtered
  9. washwashed with water (2×2.5 L), MTBE (2.5 L)
  10. customsucked dry on the sinter
  11. customdried at 65° C. in a vacuum over for 48 hours

Sources & evidence

ORD record
ord-7c5938aeed09400d8f94dff75a7421d9
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

Loading…