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 2046952Notes

Reaction equation

HRID 2046952 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-dioxolan-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 allowed to cool to rt and partitioned between EtOAc and H2O and separated. The aqueous 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. It 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. customseparated
  3. extractionThe aqueous was re-extracted with EtOAc (3×)
  4. washthe combined organic fractions were washed with H2O (2×) and brine (2×)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4b9a99ba6626410f85acb3e3617988a7
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

Loading…