Triethylamine → 3-Ethoxy-3-oxo-2-phenylpropanoic acid

2-Phenylmalonic acid monoethyl ester was prepared following the procedure in Journal of Organic Chemistry 2000, 65, 5834-5836. 2-Phenylmalonic acid monoethyl ester (1.02 g, 5.0 mmol) was dissolved in anhydrous dichloromethane (10 mL), and oxalyl chloride (0.52 mL, 6.0 mmol) was added, followed by one drop of N,N-dimethylformamide. The reaction mixture was stirred for 30 min, then concentrated, redissolved in anhydrous dichloromethane (5 mL) and added to a solution of 6-chloro-N-2-pyridinyl-3-pyridinemethanamine (i.e. the product of Example 2, Step A) (1.1 g, 5.0 mmol) and triethyl amine (0.83 mL, 6.0 mmol) in anhydrous dichloromethane (5 mL) at 0° C. The stirred reaction mixture was allowed to warm to room temperature over 30 min. The reaction mixture was poured onto a silica gel cartridge (Bond Elute® manufactured by Varian) and purified using a gradient of 0-50% ethyl acetate/hexanes. A mixture of desired product and starting amine was isolated (1.3 g of 33 mol % recovered amine/67 mol % desired product). 2-Phenylmalonic acid monoethyl ester (0.54 g, 2.6 mmol) was dissolved in anhydrous dichloromethane (3 mL), and oxalyl chloride (0.26 mL, 3.0 mmol) was added, followed by one drop of N,N-dimethylformamide. The reaction mixture was stirred until gas evolution ceased and then concentrated, redissolved in anhydrous dichloromethane (3 mL) and added to the mixture of recovered amine and desired product isolated previously. The reaction mixture was stirred for 30 min and then concentrated, and the crude residue was chromatographed as already described to give the title compound as a solid (0.9 g).

1. concentrationconcentrated
2. dissolutionredissolved in anhydrous dichloromethane (5 mL)
3. customThe stirred reaction mixture
4. additionThe reaction mixture was poured onto a silica gel cartridge (Bond Elute® manufactured by Varian)
5. custompurified
6. additionA mixture of desired product
7. customwas isolated
8. custom(1.3 g of 33 mol % recovered amine/67 mol % desired product)
9. stirringThe reaction mixture was stirred until gas evolution
10. concentrationconcentrated
11. dissolutionredissolved in anhydrous dichloromethane (3 mL)
12. additionadded to the mixture of recovered amine and desired product
13. customisolated previously
14. stirringThe reaction mixture was stirred for 30 min
15. concentrationconcentrated
16. customthe crude residue was chromatographed

ORD-Eintrag

ord-d13d8ec1dddc413d96d36fe5b47b1865

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08697707B2