Acetic Acid → 1-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 1517469Notes

Reaction equation

HRID 1517469 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[N:3]1.C([Li])CCCCC.C(O[B:18]1[O:22][C:21]([CH3:24])([CH3:23])[C:20]([CH3:26])([CH3:25])[O:19]1)(C)C.C(O)(=O)C>O1CCCC1.O>[CH3:1][N:2]1[C:6]([B:18]2[O:22][C:21]([CH3:24])([CH3:23])[C:20]([CH3:26])([CH3:25])[O:19]2)=[CH:5][CH:4]=[N:3]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 702551H-Pyrazole, 1-methyl-HCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 178506865HCID 178506865, compound

Product 1

HCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

N-Methylpyrazole (6.0 kg, 1 mol eq, limiting reagent) was charged, followed by anhydrous tetrahydrofuran (84 L, 14 rel vol) and the reaction mixture was cooled to −10° C. n-Hexyllithium (2.3 M solution in hexanes, 23.6 kg, 1.05 mol eq) was charged keeping the temperature below −5° C., followed by a line rinse of iso-hexane (1.2 L, 0.2 rel vol). The reaction mixture was stirred at below −5° C. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (14.9 kg, 1.1 mol eq) was diluted with anhydrous tetrahydrofuran (6.0 L, 1 rel vol) and was charged to the reaction keeping the temperature below 0° C. A line rinse with anhydrous tetrahydrofuran (3.0 L, 0.5 rel vol) was charged and the reaction mixture was stirred for around 30 minutes. The reaction was warmed to 25° C. A solution of glacial acetic acid (6.6 kg, 1.5 mol eq) in water (36 L, 6 rel vol) was charged to the reaction over about 30 minutes. The reaction mixture was stirred for around 30 minutes. The phases were separated and the organic layer retained. Change of solvent to acetonitrile by distillation afforded the title compound as a solution in acetonitrile. The solution yield of the title compound was determined by GC assay; 1H NMR (d6-DMSO): δ 1.31 (s, 12H), 3.98 (s, 3H), 6.62 (d, 1H, J=1.9 Hz), 7.45 (d, 1H, J=2.1 Hz) ppm.

Workup

  1. additionwas charged
  2. additionwas charged
  3. customthe temperature below −5° C.
  4. washrinse of iso-hexane (1.2 L, 0.2 rel vol)
  5. additionwas charged to the reaction
  6. customthe temperature below 0° C
  7. washA line rinse with anhydrous tetrahydrofuran (3.0 L, 0.5 rel vol)
  8. additionwas charged
  9. stirringthe reaction mixture was stirred for around 30 minutes
  10. stirringThe reaction mixture was stirred for around 30 minutes
  11. customThe phases were separated
  12. distillationChange of solvent to acetonitrile by distillation

Sources & evidence

ORD record
ord-52c78c2d4b0140a4a3dd4f78f44e14c7
Source dataset
uspto-grants-2012_07
Patent number
US08232296B2

Reaction notes

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