Trimethylboroxine → HCID 86704595, compound

HRID 1508488Notes

Reaction equation

HRID 1508488 reaction equation
I[C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)=[N:4][N:5]([CH3:11])[C:6]=1[C:7]([O:9][CH3:10])=[O:8].[CH3:20]B1OB(C)OB(C)O1>C1COCC1.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:3]2[C:2]([CH3:20])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[N:5]([CH3:11])[N:4]=2)=[CH:13][CH:14]=1

Participants

5

Reactant 2

HCID 574072Trimethylboroxine2×HCID 67516452HCID 67516452, compound

Product 1

HCID 86704595HCID 86704595, compound

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of methyl 4-iodo-3-(4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carboxylate (587.8 mg, 1.579 mmol), trimethylboroxine (883 μL, 6.32 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (103 mg, 0.158 mmol) in THF (2.6 mL) was degassed by bubbling N2 through the solution. 1N K2CO3 (2.6 mL) was added and N2 was bubbled through the mixture for 30 s. The mixture was heated in a sealed tube at 60° C. overnight. Another 4 eq. of trimethylboroxine was added and the reaction was subjected to microwave irradiation (120° C., 30 min). The reaction mixture was filtered through a plug of silica, eluted with EtOAc and the filtrate was washed with 1N aq. NaOH (2×30 mL), dried (Na2SO4) and concentrated in vacuo to afford the crude product. This was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 144 mL, gradient to 20% EtOAc in hexanes over 2394 mL) to afford methyl 3-(4-methoxyphenyl)-1,4-dimethyl-1H-pyrazole-5-carboxylate, as a colorless solid. Rf=0.33 (20% EtOAc/hexanes). LCMS calc.=261.03. found=261.12 (M+H)+. 1H NMR (600 MHz, CDCl3): δ 7.51 (d, J=8.5 Hz, 2H); 6.96 (d, J=8.5 Hz, 2H); 4.16 (s, 3H); 3.92 (s, 3H); 3.83 (s, 3H); 2.36 (s, 3H).

Workup

  1. customby bubbling N2 through the solution
  2. addition1N K2CO3 (2.6 mL) was added
  3. customN2 was bubbled through the mixture for 30 s
  4. customthe reaction was subjected to microwave irradiation (120° C., 30 min)
  5. filtrationThe reaction mixture was filtered through a plug of silica
  6. washeluted with EtOAc
  7. washthe filtrate was washed with 1N aq. NaOH (2×30 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford the crude product
  11. customThis was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 144 mL, gradient to 20% EtOAc in hexanes over 2394 mL)

Sources & evidence

ORD record
ord-380a145f5e0645f59e4b3dd614110475
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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