Hydrochloric Acid → HCID 25259740, compound

A suspension of Example 49-2 (63.5 g, 0.179 mol) in ethyl acetate (400 mL) was treated with water (200 mL) then enough 3 M HCl to bring the pH to <2. The solution was mixed and the layers were separated. The organic phase was concentrated to thick oil. The oil was dissolved in heptane (500 mL) and concentrated then redissolved in heptane (210 mL). To this solution was added N,N-dimethylformamide (1.2 g, 17.1 mmol) and oxalyl chloride (34.0 g, 0.268 mol). The solution was mixed at room temperature overnight, filtered through celite and concentrated to a residue. The crude acid chloride was dissolved in CH3CN (50 mL). To a separate vessel containing a 0° C. solution of diethyl malonate (30.0 g, 0.187 mol), and MgCl2 (17.8 g, 0.187 mol) in acetonitrile (240 mL) was added triethylamine (38.0 g, 0.376 mol). The solution was warmed to room temperature and mixed for 1 h, then cooled back to 0-10° C. The acid chloride/CH3CN solution was added over 30 minutes and the reaction mixture was heated to 50° C. for 3 h. The reaction mixture was cooled and concentrated to a thick sludge. Ethyl acetate (400 mL) and water (400 mL) were added and the pH was adjusted to 6 with concentrated HCl. The layers were separated and the organic solution was washed with 10% NaCl. The organic layer was concentrated to a thick oil then chased with heptane (300 mL) to give the title compound (assayed for 62.6 g, 93%).

1. additionThe solution was mixed
2. customthe layers were separated
3. concentrationThe organic phase was concentrated to thick oil
4. dissolutionThe oil was dissolved in heptane (500 mL)
5. concentrationconcentrated
6. dissolutionthen redissolved in heptane (210 mL)
7. additionThe solution was mixed at room temperature overnight
8. filtrationfiltered through celite
9. concentrationconcentrated to a residue
10. dissolutionThe crude acid chloride was dissolved in CH3CN (50 mL)
11. additionmixed for 1 h
12. temperaturecooled back to 0-10° C
13. temperaturethe reaction mixture was heated to 50° C. for 3 h
14. temperatureThe reaction mixture was cooled
15. concentrationconcentrated to a thick sludge
16. additionEthyl acetate (400 mL) and water (400 mL) were added
17. customThe layers were separated
18. washthe organic solution was washed with 10% NaCl
19. concentrationThe organic layer was concentrated to a thick oil

ORD record

ord-298f72fb287e46269c89cda671835e3f

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538105B2