Methyl 3-hydroxypivalate → Methyl 2,2-dimethyl-3-oxopropanoate

To a solution of 2,2-dimethyl-3-oxo-propionic acid methyl ester (WHSS0374-001) (0.90 g; 5.44 mmol) in 1,2-dichloroethane (20 mL) was added 2-[4-(2,6-dichloro-benzyloxy)-phenyl]-morpholine (0.91 g, 2.7 mmol) and NaBH(OAc)3 (1.62 g; 7.62 mmol). The resulting mixture was stirred overnight at RT, and subsequently treated with 5% aqueous NaHCO3 (10 mL) and extracted with CH2Cl2 (3×30 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O/hexanes 1:1) to afford 3-{2-[4-(2,6-dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-2,2-dimethyl-propionic acid methyl ester (1.12 g) as a clear colourless oil. The required 2,2-dimethyl-3-oxo-propionic acid methyl ester was prepared as follows: To a solution of 2,2-dimethyl-3-hydroxypropionic acid methyl ester (10.00 g; 75.7 mmol) in CH2Cl2 (200 mL) was added pyridinium chloroformate (28.54 g; 132.4 mmol) in small portions, at 0° C. The reaction mixture was allowed to slowly warm to RT and stirred overnight. Subsequently, the mixture was diluted with CH2Cl2, filtered over kieselguhr, and concentrated in vacuo. The remaining oil was purified by column chromatography (SiO2, hexanes/Et2O 7:3) to afford 2,2-dimethyl-3-oxo-propionic acid methyl ester (5.59 g)

1. customThe required 2,2-dimethyl-3-oxo-propionic acid methyl ester was prepared
2. customat 0° C
3. filtrationfiltered over kieselguhr
4. concentrationconcentrated in vacuo
5. customThe remaining oil was purified by column chromatography (SiO2, hexanes/Et2O 7:3)

ORD record

ord-d070b9aff810435d806bd5192b2e7b19

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273017B2