Dichloromethane → HCID 75274482, compound

Zn solid was activated just prior to perform Reformatsky reaction as followed: Zn dust was stirred at r.t. in 2 M aqueous HCl solution until the bubbling ceased (≈40 min for 15 g Zn). The solid was then filtered and washed with water (50 mL), the EtOH (50 mL), acetone (50 mL), then Et2O (50 mL) and the thin solid was heated using an air gun under vacuum to complete drying. Reformasky reaction: to a suspension of such activated Zn* solid (2.29 g, 35 mmol) in dry THF (70 mL) warmed to reflux temperature under argon was added dropwise through the condenser over 40 min a mixture of ethylbromoacetate (1.75 mL, 15 mmol) and diketone (1) (0.761 g, 5 mmol) in dry THF (125 mL). The green mixture was stirred at reflux temperature for 5 h, then cooled to r.t. and hydrolyzed by quite slow addition of saturated aqueous NH4Cl solution (until pH=5-6): the resulting colorless solution with the Zn solid floating around was stirred for 10 min at r.t. before extraction with DCM (3×80 mL). The combined org. layers were washed with saturated solution of NaHCO3 (80 mL), then brine (80 mL), then water (80 mL), dried with MgSO4 and concentrated under reduced pressure to afford an orange oil. This crude product was then filtered trough a plug of silica gel and washed with AcOEt/cyclohexane mixtures, then with pure AcOEt to afford the desired acetal (2) as yellow oil pure enough to carry on the synthesis. A purer product can be obtained as white crystals (1.044 g, 87%) after flash chromatography (AcOEt/cyclohexane 4/6, v/v).

1. customreaction
2. filtrationThe solid was then filtered
3. washwashed with water (50 mL)
4. temperaturethe EtOH (50 mL), acetone (50 mL), then Et2O (50 mL) and the thin solid was heated
5. customto complete drying
6. customReformasky reaction
7. temperaturewarmed
8. temperatureto reflux temperature under argon
9. additionwas added dropwise through the condenser over 40 min
10. temperatureat reflux temperature for 5 h
11. washlayers were washed with saturated solution of NaHCO3 (80 mL)
12. dry with materialbrine (80 mL), then water (80 mL), dried with MgSO4
13. concentrationconcentrated under reduced pressure
14. customto afford an orange oil
15. filtrationThis crude product was then filtered trough a plug of silica gel
16. washwashed with AcOEt/cyclohexane mixtures

ORD record

ord-7074734c321f4ea8b411b5eba1b793f3

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290750B2