Phosphoric Acid → Tert-butyl 6-chloropyridine-3-carboxylate

A mixture of 6-chloronicotinic acid (12.0 g, 76 mmol) and thionyl chloride (65 mL) was heated at reflux for 3.0 h. The excess thionyl chloride was removed under reduced pressure, and the residual liquid was diluted with dichloromethane (20 mL) and then added to a solution of tert-butyl alcohol (71 mL, 760 mmol) in dichloromethane (40 mL). To the mixture was added triethylamine (31.7 mL, 760 mmol) and N,N-dimethylpyridine (0.5 g, 4.0 mmol), and the reaction mixture was stirred overnight (14 h) at reflux under nitrogen. The solution was diluted with dichloromethane (200 mL), washed with a saturated aqueous solution of sodium bicarbonate (3×100 mL), washed with water (3×100 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure provided Preparation 3 (11.4 g, 70.3%) as a yellow solid. The product had an analytical HPLC retention time=3.18 min. (Column: YMC ODS 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.2% H3PO4; Solvent B=90% MeOH, 10% H2O, 0.2% H3PO4) and a LCMS M+1=214. The purity of the product was about 96%. The major impurity was the iso-propyl 6-chloronicotinate with an analytical HPLC retention time=2.88 min. and a LC/MS M+1=200.

1. temperaturewas heated
2. temperatureat reflux for 3.0 h
3. customThe excess thionyl chloride was removed under reduced pressure
4. additionthe residual liquid was diluted with dichloromethane (20 mL)
5. temperatureat reflux under nitrogen
6. washwashed with a saturated aqueous solution of sodium bicarbonate (3×100 mL)
7. washwashed with water (3×100 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationConcentration under reduced pressure
10. customprovided

ORDレコード

ord-dae4d64143ca4b8faa1e96032eb9aeb8

出典データセット

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07186727B2