Acetaldehyde → HCID 86706066, compound

Temperature

-78 °C

A solution of N,N-diisopropylamine (1.67 g, 2.3 mL, 16.5 mmol) in anhydrous tetrahydrofuran (10 mL) was stirred at −78° C. under nitrogen. n-Butyllithium (6.6 mL, 16.5 mmol, 2.5 M solution in hexane) was added dropwise and the reaction mixture was stirred at −78° C. for 30 minutes. A solution of [1,4]dioxane-2-carboxylic acid methyl ester (1.61 g, 11 mmol) in tetrahydrofuran (10 mL) was added and the reaction mixture was stirred at −78° C. for 30 minutes. Acetaldehyde (1.45 g, 1.8 mL, 33 mmol) was added in one portion. The cooling bath was removed and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was cooled to 5° C. and ice-cold 1 M hydrochloric acid was added to acidify the reaction mixture to pH 2. Sodium chloride was added to saturate the solution and the mixture was extracted with diethyl ether (4×). 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 pentane/diethyl ether 1:1 to 0:1 to afford the title compound (1.49 g, 71%), as an oil, and as a 3:1 mixture of diastereoisomers. LCMS (m/z) 213.2 [M+H], Tr=0.62 min.

1. stirringthe reaction mixture was stirred at −78° C. for 30 minutes
2. customThe cooling bath was removed
3. stirringthe reaction mixture was stirred at room temperature for 30 minutes
4. temperatureThe reaction mixture was cooled to 5° C.
5. additionice-cold 1 M hydrochloric acid was added
6. additionSodium chloride was added
7. concentrationto saturate the solution
8. extractionthe mixture was extracted with diethyl ether (4×)
9. washwashed with brine
10. filtrationThe organic solution was filtered through a hydrophobic frit
11. customthe filtrate was evaporated
12. customThe residue was purified by silica gel chromatography

ORD record

ord-3cb7088c0b4142e48cc7918f22598548

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062092B2