Potassium Phosphate, Tribasic → Benzoic acid, 3-methoxy-4-(1H-pyrazol-4-yl)-, methyl ester

HRID 2273992Notes

Reaction equation

HRID 2273992 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[O:12][CH3:13].CC1(C)C(C)(C)OB([C:22]2[CH:23]=[N:24][N:25](C(OC(C)(C)C)=O)[CH:26]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:13][O:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[C:22]1[CH:23]=[N:24][NH:25][CH:26]=1)[C:6]([O:8][CH3:9])=[O:7]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 14570117Methyl 4-bromo-3-methoxybenzoateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

Product 1

HCID 90354000Benzoic acid, 3-methoxy-4-(1H-pyrazol-4-yl)-, methyl ester

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 4-bromo-3-methoxybenzoate (1.32 g, 5.39 mmol) in dioxane (30 mL) and water (5 mL) were added tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (1.901 g, 6.46 mmol), potassium phosphate (2.86 g, 13.47 mmol) and PdCl2(dppf) (0.197 g, 0.269 mmol) at RT. The reaction was stirred under argon at 100° C. for 3 hrs. The reaction mixture was diluted with EtOAc, washed with H2O. The organic phase was dried over sodium sulfate, filtered and concentrated. The residue was dissolved in DCM (10 mL) and TFA (5 mL) was added. The reaction was stirred at RT for 1.5 hrs. Solvent was removed. The residue was taken into EtOAc, which was washed with NaHCO3 (3×) and brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by normal phase chromatography. Desired product was isolated as white solid (0.86 g, 69% yield). LCMS (ESI) m/z: 233.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.13 (s, 2H), 7.73-7.66 (m, 1H), 7.66-7.56 (m, 2H), 3.98 (s, 3H), 3.94 (s, 3H).

Workup

  1. washwashed with H2O
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in DCM (10 mL)
  6. additionTFA (5 mL) was added
  7. stirringThe reaction was stirred at RT for 1.5 hrs
  8. customSolvent was removed
  9. washwas washed with NaHCO3 (3×) and brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified by normal phase chromatography

Sources & evidence

ORD record
ord-533d323ac99a4726a23ec985d652f796
Source dataset
uspto-grants-2015_09
Patent number
US09126944B2

Reaction notes

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