2-Bromo-5-methylpyridine → HCID 178426494, compound

HRID 707430Notes

Reaction equation

[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][CH2:3]1.Br[C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][N:18]=1.C([O-])(=O)C.[Cs+]>CS(C)=O.O.[Cu]>[C:11]([O:10][C:9](=[O:15])[NH:8][C@H:5]1[CH2:6][CH2:7][C@@H:2]([NH:1][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][N:18]=2)[CH2:3][CH2:4]1)([CH3:12])([CH3:14])[CH3:13]

Participants

Conditions

Temperature: 100 °C

Procedure

To a round bottomed flask was added cis tert-butyl 4-aminocyclohexylcarbamate (0.5020 g, 2.342 mmol, Matrix Scientific), 2-bromo-5-methylpyridine (0.484 g, 2.81 mmol, Acros Organics), copper (0.012 g, 0.187 mmol, Fisher Scientific), and cesium acetate (2.79 g, 14.52 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO (2.93 ml) to stir at 100° C. for 17 h. The reaction mixture was diluted with water and extracted with CH2Cl2. The organic extract was washed with ammonium hydroxide, water, saturated NaCl, dried over MgSO4, filtered and concentrated 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 10% to 100% EtOAc in hexane, to provide the title compound (279.5 mg, 0.915 mmol, 39.1% yield). LCMS showed product peak at 1.56 min (m+1=306.0).

Workup

extractionextracted with CH2Cl2
extractionThe organic extract
washwas washed with ammonium hydroxide, water, saturated NaCl
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customchromatographed through a Biotage SNAP HP-silica gel column (50 g)
washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record: ord-815a9c84603f42e29974eb629499fb85
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174992B2

Reaction notes

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