Oxalyl chloride → 1,1-Dimethylethyl 2-[(6-fluoro-2-pyridinyl)carbonyl]hydrazinecarboxylate

6-Fluoro-2-pyridinecarboxylic acid (2.83 g, 20.06 mmol, CAS[402-69-7], commercially available e.g. from Sigma-Aldrich or Apollo Scientific) was dissolved in Dichloromethane (DCM) (100 mL) at 0° C. Oxalyl chloride (2.107 mL, 24.07 mmol) and a drop of N,N-dimethylformamide (DMF) was added and the mixture was stirred for 2 hours. The solvents were removed in vacuo and azeotroped with toluene (3×20 ml). The residue was dissolved in dichloromethane (DCM) (100 ml) whereupon 1,1-dimethylethyl hydrazinecarboxylate (2.92 g, 22.06 mmol) and N,N-diisopropylethylamine (DIPEA) (7.71 mL, 44.1 mmol) were added. The mixture was stirred at room temperature for 3 hours and concentrated in vacuo. The residue was partitioned between ethyl acetate (100 ml) and saturated sodium bicarbonate solution (50 ml). The aqueous phase was extracted with ethyl acetate (3×100 ml), the combined organic extracts were washed with brine (50 ml), were dried over anhydrous sodium sulphate and were concentrated in vacuo. The residue was purified by flash chromatography (Biotage SP4, 40+M, 0-100% ethyl acetate/iso-hexane) to afford 1,1-dimethylethyl 2-[(6-fluoro-2-pyridinyl)carbonyl]hydrazinecarboxylate (5.04 g, 19.75 mmol).

1. customThe solvents were removed in vacuo
2. customazeotroped with toluene (3×20 ml)
3. additionwere added
4. stirringThe mixture was stirred at room temperature for 3 hours
5. concentrationconcentrated in vacuo
6. customThe residue was partitioned between ethyl acetate (100 ml) and saturated sodium bicarbonate solution (50 ml)
7. extractionThe aqueous phase was extracted with ethyl acetate (3×100 ml)
8. washthe combined organic extracts were washed with brine (50 ml)
9. dry with materialwere dried over anhydrous sodium sulphate
10. concentrationwere concentrated in vacuo
11. customThe residue was purified by flash chromatography (Biotage SP4, 40+M, 0-100% ethyl acetate/iso-hexane)

ORD record

ord-75e29fb92f034e539707b0ee384577c7

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501946B2