Pyrrolidine → 2-(Pyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

HRID 1852406Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([B:10]2[O:18][C:15]([CH3:17])([CH3:16])[C:12]([CH3:14])([CH3:13])[O:11]2)[CH:6]=[CH:7][C:8]=1F)#[N:2].[NH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1>CN1C(=O)CCC1>[N:19]1([C:8]2[CH:7]=[CH:6][C:5]([B:10]3[O:18][C:15]([CH3:17])([CH3:16])[C:12]([CH3:14])([CH3:13])[O:11]3)=[CH:4][C:3]=2[C:1]#[N:2])[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

Conditions

Temperature: 140 °C

Procedure

3-Cyano-4-fluorophenyl-boronic acid pinacol ester (250 mg, 1.01 mmol) was dissolved in NMP (4 mL). Pyrrolidine (415 μL, 5.05 mmol) was added and the mixture heated at 140° C. in the microwave (300 W, stirring) for 5 minutes. The reaction was repeated 14 more times. The 15 reaction mixtures were combined and the solvent evaporated in vacuo (Genevac™). The residue was dissolved in EtOAc (200 mL) and the solution washed with saturated brine solution (2×75 mL). The organic phase was dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (40-63 mesh silica gel, 90% isohexane-EtOAc) to provide the title compound as an off-white solid (2.84 g, 63%); LC-MS, Rt=3.33 min (MeOH-FA method), m/z 298 (MH+).

Workup

customThe 15 reaction mixtures
customthe solvent evaporated in vacuo (Genevac™)
dissolutionThe residue was dissolved in EtOAc (200 mL)
washthe solution washed with saturated brine solution (2×75 mL)
dry with materialThe organic phase was dried (MgSO4)
filtrationfiltered
customthe solvent evaporated in vacuo
customThe crude product was purified by flash column chromatography (40-63 mesh silica gel, 90% isohexane-EtOAc)

Sources & evidence

ORD record: ord-e15cba79c300497f8f68128b85169c53
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962609B2

Reaction notes

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