Reaction equation
[Br:1][C:2]1[C:3]([CH3:8])=[N:4][NH:5][C:6]=1[CH3:7].Br[CH2:10][C:11]1([CH3:15])[CH2:14][O:13][CH2:12]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[Br:1][C:2]1[C:3]([CH3:8])=[N:4][N:5]([CH2:10][C:11]2([CH3:15])[CH2:14][O:13][CH2:12]2)[C:6]=1[CH3:7]Participants
Conditions
- Temperature
- 70 °C
Procedure
To a 4 mL vial equipped with a magnetic stir bar were added 4-bromo-3,5-dimethyl-1H-pyrazole (150 mg, 0.857 mmol), 3-(bromomethyl)-3-methyloxetane (283 mg, 1.714 mmol), K2CO3 (355 mg, 2.57 mmol), and acetonitrile (2 mL). The contents of the vial were stirred to give a white suspension. The vial was heated in a sand bath to 70° C. for 24 hours, and the reaction mixture was subsequently partitioned between water (15 mL) and ethyl acetate (20 mL). The layers were separated and the aqueous layer was back-extracted with ethyl acetate (20 mL). The combined organic layers were concentrated and the residue was purified via flash chromatography (4 g column) eluting with a gradient of 0-70% EtOAc in heptanes. The pure fractions were combined and concentrated to give the title compound as a clear liquid (110 mg, 49.5%).
Workup
- customTo a 4 mL vial equipped with a magnetic stir bar
- customto give a white suspension
- customthe reaction mixture was subsequently partitioned between water (15 mL) and ethyl acetate (20 mL)
- customThe layers were separated
- extractionthe aqueous layer was back-extracted with ethyl acetate (20 mL)
- concentrationThe combined organic layers were concentrated
- customthe residue was purified via flash chromatography (4 g column)
- washeluting with a gradient of 0-70% EtOAc in heptanes
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-ad38f0e623d747e39deab37cc0c76e07
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434743B2
Linked notes
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