Formaldehyde → HCID 85762566, compound

Temperature

40 °C

A solution of 3-oxo-butyric acid tert-butyl ester (15.8 g, 100 mmol) and aqueous formaldehyde (37% solution in water, 18 mL, 230 mmol) in 1,4-dioxane (50 mL) was stirred at 0° C. under nitrogen. A solution of triethylamine (505 mg, 0.7 mL, 5 mmol) in tetrahydrofuran (5 mL) was added dropwise and the reaction mixture was stirred at 40° C. for 1 h and then at room temperature for 20 h. The majority of the solvent was evaporated, water was added and the mixture was extracted with ethyl acetate. The organic extracts were combined and washed with brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 7:3 to 1:1 to afford 2,2-bis-hydroxymethyl-3-oxo-butyric acid tert-butyl ester (8.67 g, 40%) as a clear oil. 1H NMR (300 MHz, d6-DMSO) 61.38 (s, 9H), 2.07 (s, 3H), 3.81-3.86 (m, 4H), 4.77 (t, J=5.1 Hz, 2H). LCMS (m/z) 217.0 [M−H], Tr=1.45 min.

1. waitat room temperature for 20 h
2. customThe majority of the solvent was evaporated
3. additionwater was added
4. extractionthe mixture was extracted with ethyl acetate
5. washwashed with brine
6. filtrationThe organic solution was filtered through a hydrophobic frit
7. customthe filtrate was evaporated
8. customThe residue was purified by silica gel chromatography

ORD record

ord-7f94116aa2e64bcdafccf66c4ffa67e2

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062092B2