Ethyl benzoylformate → (+-)-Cyclohexylphenylglycolic acid

Temperature

0 °C

A 250 mL round-bottom flask was charged with anhydrous THF (120 mL) at room temperature and then cooled to 0° C. with water/ice bath. Cyclohexylmagnesium chloride solution (2.0 M in ethyl ether) (56 mL, 112 mmol) was added. A solution of ethyl benzoylformate (14.89 g, 79.41 mmol) in THF (20 mL) was added dropwise over 30 minutes. More of THF (10 mL) was added to wash the addition funnel. The resulting mixture was stirred at 0° C. for 15 minutes, and then at room temperature for three hours. The reaction mixture was poured into saturated aqueous ammonium chloride (150 mL). Water (15 mL) was added. The mixture was concentrated to remove the organic solvents. The remaining solution was extracted with EtOAc (2×100 mL). The extraction was washed with brine, dried over sodium sulfate, concentrated to afford a slight green residue. The residue was purified with flash column chromatography on silica gel using 0-8% EtOAc/hexane (20 CV, 40 M column, biotage) to afford 14.955 g of product in 72% yield. 1H-NMR (400 MHz, CDCl3).

1. washto wash the addition funnel
2. waitat room temperature for three hours
3. additionThe reaction mixture was poured into saturated aqueous ammonium chloride (150 mL)
4. additionWater (15 mL) was added
5. concentrationThe mixture was concentrated
6. customto remove the organic solvents
7. extractionThe remaining solution was extracted with EtOAc (2×100 mL)
8. extractionThe extraction
9. washwas washed with brine
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated
12. customto afford a slight green residue
13. customThe residue was purified with flash column chromatography on silica gel using 0-8% EtOAc/hexane (20 CV, 40 M column, biotage)

ORD record

ord-d2a4f9545c7545179e39e5f4e45d9810

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389759B2