Potassium Carbonate → Tert-butyl 3-(2,6-dichloro-4-pyridyl)-2,5-dihydropyrrole-1-carboxylate

HRID 1057046Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([Cl:9])[N:3]=1.CC1(C)C(C)(C)OB([C:18]2[CH2:19][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:21][CH:22]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[Cl:1][C:2]1[CH:7]=[C:6]([C:22]2[CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]=2)[CH:5]=[C:4]([Cl:9])[N:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a mixture of 2,6-dichloro-4-iodo-pyridine (500 mg, 1.826 mmol), tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,5-dihydropyrrole-1-carboxylate (646.7 mg, 2.191 mmol, 1.2 equiv.), potassium carbonate (510 mg, 3.651 mmol, 2 equiv.), and PD(dppf)Cl2 DCM (223.6 mg, 0.274 mmol, 0.15 equiv.) in 1,4-dioxane (6 mL) and water (2 mL) was capped in a large CEM vial, de-gassed with N2, heated in oil bath @ 65° C. o/n. It was diluted with water, extracted with EtOAc (2×50 mL), dried over Na2SO4, filtered, concentrated in vacuo. Purification by column chromatography (ISCO), 40 g column, eluded with 0-10% EtOAc/Heptane to afford 304 mg (52.8%) of product as white foam. 1H NMR (400 MHz, CDCl3) δ 7.42 (s, 0.5H), 7.22 (s, 0.5H), 7.04 (s, 2H), 3.93 (s, 2H), 2.90 (s, 2H), 1.53 (s, 9H). LC-MS: m/z=316 (M+H+).

Workup

customwas capped in a large CEM vial
customde-gassed with N2
additionIt was diluted with water
extractionextracted with EtOAc (2×50 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by column chromatography (ISCO), 40 g column

Sources & evidence

ORD record: ord-93eff2c19e1046c98e457e355d8d44d2
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09399636B2

Reaction notes

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