Cesium carbonate → Tert-butyl (6-chloro-5-fluoropyridin-3-yl)carbamate

HRID 60234

Reaction equation

Br[C:2]1[CH:3]=[C:4]([F:9])[C:5]([Cl:8])=[N:6][CH:7]=1.[C:10](=[O:17])([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[NH2:11].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[C:13]([O:12][C:10](=[O:17])[NH:11][C:2]1[CH:7]=[N:6][C:5]([Cl:8])=[C:4]([F:9])[CH:3]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 85 °C

Procedure

A degassed mixture of 5-bromo-2-chloro-3-fluoropyridine (22.5 g, 107 mmol), tert-butyl carbamate (13.8 g, 117.5 mmol), tris(dibenzylideneacetone) dipalladium(0) (2.95 g, 3.2 mmol), XantPhos (2.48 g, 4.28 mmol) and cesium carbonate (69.7 g, 214 mmol) in dioxane (340 mL) was heated at 85° C. for 24 hours. The reaction mixture was cooled to ambient temperature and the resultant solid was removed by filtration. The resultant solid was washed with ethyl acetate followed by dichloromethane and the filtrate was combined and concentrated in-vacuo to afford a residue that was purified by flash chromatography (silica: cyclohexane to 25% ethyl acetate/cyclohexane) to afford the title compound as a pale yellow solid (22.6 g, 86%). 1H NMR (300 MHz, CDCl3): 8.04 (dd, J=10.1, 2.4 Hz, 1H), 7.98 (d, J=2.4 Hz, 1H), 6.62 (s, 1H), 1.53 (s, 9H).

Workup

temperatureThe reaction mixture was cooled to ambient temperature
customthe resultant solid was removed by filtration
washThe resultant solid was washed with ethyl acetate
concentrationconcentrated in-vacuo
customto afford a residue that
customwas purified by flash chromatography (silica: cyclohexane to 25% ethyl acetate/cyclohexane)

Sources & evidence

ORD record: ord-2aad88eff7364f1f9f9968439896e0fc
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Linked notes

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