Chloroacetone → 3-Chloro-4,4-diethoxybutan-2-one

Temperatur

-78 °C

A solution of BF3.Et2O (9.35 mL; 108 mmol; 2 eq.) in DCM (100 mL) was added dropwise at −30° C. over 50 minutes to diethoxymethoxy-ethane (18 mL; 108 mmol; 2 eq.). The reaction mixture was stirred at this temperature for a further 40 minutes then allowed to return to room temperature and was stirred at room temperature for 1 hour. After cooling down to −78° C., 1-chloro-propan-2-one (4.3 mL; 54 mmol; 1 eq.) was added dropwise followed by DIEA (28 mL; 162 mmol; 3 eq.) at such a rate to keep the temperature below −70° C. The resulting mixture was stirred at −70° C. for one hour then poured onto sat. aq. NaHCO3. The two layers were separated and the aqueous phase extracted with DCM. The combined organics were washed with cold diluted H2SO4 then water, dried over magnesium sulfate and concentrated in vacuo to afford the title compound (6 g, 48%) as a brown oil which was used without further purification. 1H NMR (DMSO-d6) δ 4.81 (d, J=6.0 Hz, 1H), 4.64 (d, J=6.0 Hz, 2H), 3.70-3.44 (m, 4H), 2.25 (s, 3H), 1.30-1.17 (m, 6H).

1. customto return to room temperature
2. stirringwas stirred at room temperature for 1 hour
3. customthe temperature below −70° C
4. stirringThe resulting mixture was stirred at −70° C. for one hour
5. customThe two layers were separated
6. extractionthe aqueous phase extracted with DCM
7. washThe combined organics were washed with cold diluted H2SO4
8. dry with materialwater, dried over magnesium sulfate
9. concentrationconcentrated in vacuo

ORD-Eintrag

ord-e2fd0601550546a4a20106b07ede4ccd

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09403835B2