Phosphorus oxychloride → Methyl 5-chloro-3-methylpyrazine-2-carboxylate

Temperature

100 °C

In a 1-L flask, the crude 3-(methoxycarbonyl)-2-methylpyrazine 1-oxide (step 2, 17.77 g, 106 mmol) was dissolved in DMF (300 mL). Neat phosphoryl trichloride (29.6 mL, 317 mmol) was added. The reaction mixture was heated to 100° C. After 1 h, the reaction mixture was concentrated to remove most of the DMF. The flask was cooled in an ice water bath, and 1 M aqueous Na2CO3 (300 mL) was added slowly, followed by 80% EtOAc-hexane (400 mL). The mixture was filtered through Celite. The resulting filtrate was partitioned and the aqueous phase was extracted further with 80% EtOAc-hexane (2×250 mL). The combined organic layers were dried over MgSO4 and concentrated. The material was purified through silica gel using 11% EtOAc-hexane to afford the title compound (4.29 g, 23 mmol, 22%). MS m/z=187 (M+H).

1. concentrationthe reaction mixture was concentrated
2. customto remove most of the DMF
3. temperatureThe flask was cooled in an ice water bath
4. addition1 M aqueous Na2CO3 (300 mL) was added slowly
5. filtrationThe mixture was filtered through Celite
6. customThe resulting filtrate was partitioned
7. extractionthe aqueous phase was extracted further with 80% EtOAc-hexane (2×250 mL)
8. dry with materialThe combined organic layers were dried over MgSO4
9. concentrationconcentrated
10. customThe material was purified through silica gel using 11% EtOAc-hexane

ORD record

ord-5bc7e28e35b54f74a9d4b00b1742990a

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309263B2