Acetaldehyde → 10150-92-2

Temperature

-10 °C

2,2,6,6-Tetramethylpiperidine (74.16 g, 0.525 mot) is dissolved in THF (600 ml) and cooled to −45° C. nBuLi is added (0.022 mol g−1 in hexane, 228.3 g, 0.500 mol) and is allowed to warm to −10° C. The reaction mixture is cooled to −70° C. Then ethyl propiolate (49.05 g, 0.500 mol) is added dropwise over 25 min at ≦−66° C. After additional stirring for 70 min at −72° C., acetaldehyde (23.35 g, 0.530 mol) in cold THF (30 ml) is added dropwise in 30 min at ≦−67° C. After stirring at −72° C. for 1 hour the reaction mixture is quenched with 2 M HCl (700 ml) and extracted with tBuOMe (650 and 400 ml). The organic phases are washed with saturated NaHCO3 (200 ml) and brine (3×125 ml) successively. The combined organic phases are dried with Na2SO4 and evaporated under reduced pressure at 40° C. Filtration over SO2 (150 g) with tBuOMe:heptane fraction (0.5 l) and tBuOMe (0.2 l) yields crude 20 (rac-Ethyl 4-hydroxypent-2-enoate) (6744 g, 90%, HPLC: ˜90 area %) as a brown oil. The crude product is used in the next step without further purification. 1H-NMR- and GC-analysis corresponded to an analogous synthesis of 20 (rac-Ethyl 4-hydroxypent-2-inoate) with LDA as base.

1. temperatureThe reaction mixture is cooled to −70° C
2. stirringAfter stirring at −72° C. for 1 hour the reaction mixture
3. customis quenched with 2 M HCl (700 ml)
4. extractionextracted with tBuOMe (650 and 400 ml)
5. washThe organic phases are washed with saturated NaHCO3 (200 ml) and brine (3×125 ml) successively
6. dry with materialThe combined organic phases are dried with Na2SO4
7. customevaporated under reduced pressure at 40° C
8. filtrationFiltration over SO2 (150 g) with tBuOMe

ORD record

ord-3320f7f0c7ba4c9a887c0eedb55ba6b6

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288566B2