4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 511278Notes

Reaction equation

HRID 511278 reaction equation
[CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.C1(C)C=CC(S(O[CH2:25][C@H:26]2[CH2:30][O:29][C:28]([CH3:32])([CH3:31])[O:27]2)(=O)=O)=CC=1>CN(C=O)C>[CH3:31][C:28]1([CH3:32])[O:27][C@@H:26]([CH2:25][N:12]2[CH:13]=[C:9]([B:4]3[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]3)[CH:10]=[N:11]2)[CH2:30][O:29]1

Participants

4

Reactant 2

HCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 6993835(R)-(-)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-Toluenesulfonate

Product 1

HCID 67253006(S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(4,4,5,5-Tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (9.24 g, 47.6 mmol), (R)-(−)-(2,2-Dimethyl-1,3-di oxolan-4-yl)methyl p-toluenesulfonate (15.00 g, 52.38 mmol) and CsHCO3 (23.3 g, 71.4 mmol) in anhydrous DMF (236 mL) was heated to 100° C. for 16 h. The reaction mixture was cooled to rt and partitioned between EtOAc and H2O. The aqueous layer was re-extracted with EtOAc (3×) and the combined organic fractions were washed with H2O (2×) and brine (2×), dried over Na2SO4, filtered and concentrated in vacuo resulting in the title compound as an orange oil which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3): δ=1.31 (s, 12H), 1.33 (s, 3H), 1.39 (s, 3H), 3.78 (dd, J=8.8, 5.9 Hz, 1H), 4.07 (dd, J=8.8, 6.2 Hz, 1H), 4.23-4.35 (m, 2H), 4.47 (quint, J=5.8 Hz, 1H), 7.78 (s, 1H), 7.81 (s, 1H).

Workup

  1. custompartitioned between EtOAc and H2O
  2. extractionThe aqueous layer was re-extracted with EtOAc (3×)
  3. washthe combined organic fractions were washed with H2O (2×) and brine (2×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a7bada15ee7e42f0b52c54368ceed8c1
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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