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-8d4f734d1d2b460e919e0ff8ae7846ee

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045441B2