Sodium t-butoxide → HCID 178454102, compound

HRID 707427Notes

Reaction equation

[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]1[CH2:11][C@@H:10]([NH:12][C:13](=[O:24])[C:14]([C:17]2[C:22](Cl)=[N:21][CH:20]=[CH:19][N:18]=2)([CH3:16])[CH3:15])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+]>CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.CC(OC)(C)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1>[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]1[CH2:11][C@@H:10]([N:12]2[C:22]3=[N:21][CH:20]=[CH:19][N:18]=[C:17]3[C:14]([CH3:16])([CH3:15])[C:13]2=[O:24])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a glass microwave reaction vessel was added tert-butyl(cis-3-(2-(3-chloropyrazin-2-yl)-2-methylpropanamido)cyclobutyl)carbamate (0.8210 g, 2.226 mmol), RuPhos Precatalyst (0.097 g, 0.134 mmol, Strem Chemicals), and sodium tert-butoxide (0.428 g, 4.45 mmol, Sigma-Aldrich Chemical Company, Inc.) in dry dioxane (2.226 ml) to stir at 80° C. for 24 h. The solvent was evaporated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (50 g), eluting with a gradient of 40% to 100% EtOAc in hexane, to provide the title compound (0.1812 g, 0.545 mmol, 24.49% yield). LCMS showed product peak at 2.060 min (m+1=333.0). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.31 (s, 3 H) 1.39 (s, 5 H) 2.52-2.58 (m, 1 H) 2.80 (qd, J=9.16, 2.64 Hz, 1 H) 3.68-3.83 (m, 1 H) 4.34-4.47 (m, 1 H) 7.21 (d, J=6.85 Hz, 1 H) 8.13-8.18 (m, 1 H)

Workup

customTo a glass microwave reaction vessel
customThe solvent was evaporated in vacuo
customchromatographed through a Biotage SNAP HP-silica gel column (50 g)
washeluting with a gradient of 40% to 100% EtOAc in hexane

Sources & evidence

ORD record: ord-c985d6331d324d86af044b4cccd3c1e9
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174992B2

Reaction notes

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