Hydrochloric Acid → 4-(5,6-Dichloropyridine-3-carbonyl)morpholine

Oxalyl chloride (3.2 mL; 36.0 mmol) was added to a solution of 5,6 dichloronicotinic acid (5.76 g; 30.0 mmol) and 4M hydrogen chloride in dioxane (7.5 mL; 30 mmol) in DCM (50 mL). The mixture was stirred at RT for 18 hours, the DCM evaporated in vacuo, the residue azeotroped with toluene (2×15 mL) and added to a solution of morpholine (3.1 mL; 36.0 mmol) and triethylamine (10.0 mL; 72 mmol) in DCM (150 mL). The mixture was stirred at RT for 18 hours, the DCM evaporated in vacuo, and the residue partitioned between water (75 mL) and ethyl acetate (100 mL). The organic layer was washed with brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 50% ethyl acetate in isohexane, to give the desired compound (7.1 g).

1. customthe DCM evaporated in vacuo
2. customthe residue azeotroped with toluene (2×15 mL)
3. stirringThe mixture was stirred at RT for 18 hours
4. customthe DCM evaporated in vacuo
5. customthe residue partitioned between water (75 mL) and ethyl acetate (100 mL)
6. washThe organic layer was washed with brine
7. dry with materialdried (MgSO4)
8. customevaporated to a residue which
9. customwas chromatographed on silica
10. washeluting with 50% ethyl acetate in isohexane

ORD record

ord-1a215bd108e24d4bbd070ff7b05add49

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07977328B2