Dimethylformamide → tert-Butyl 4-chloro-3-formylpyridin-2-ylcarbamate

HRID 1670330Notes

Reaction equation

[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.CN([CH:24]=[O:25])C>C1COCC1>[Cl:14][C:12]1[CH:11]=[CH:10][N:9]=[C:8]([NH:7][C:6](=[O:15])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[C:13]=1[CH:24]=[O:25]

Participants

Conditions

Temperature: -78 °C

Procedure

To (4-chloro-pyridin-2-yl)-carbamic acid tert-butyl ester (CB Research and Development Inc., 2.0 g, 8.75 mmol) in THF (18 mL) under nitrogen at −78° C., was added n-BuLi (13.7 mL, 21.9 mmol, 1.6 M in hexanes) dropwise. After stirring at −78° C. for 45 min, a solution of DMF (1.93 mL) in THF (2 mL) was added dropwise. The reaction was stirred at −78° C. for 30 min and was then allowed to warm slowly to room temperature. The reaction was quenched with 1N aq HCl solution and then basified with saturated aqueous sodium bicarbonate solution (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (EtOAc) to afford the title compound (0.95 g, 42%) as a white solid. 1H NMR (DMSO-d6) δ 10.44 (s, 1H), 10.13 (s, 1H), 8.47 (d, 1H, J=5.2 Hz), 7.40 (d, 1H, J=5.6 Hz), 1.48 (s, 9H).

Workup

stirringThe reaction was stirred at −78° C. for 30 min
temperatureto warm slowly to room temperature
customThe reaction was quenched with 1N aq HCl solution
extractionextracted with ethyl acetate (3×50 mL)
dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
concentrationconcentrated in vacuo
customThe crude product was purified by flash column chromatography on silica gel (EtOAc)

Sources & evidence

ORD record: ord-9c047daa376647afa914508a3aae86a9
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989477B2

Reaction notes

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