Methyl diethylphosphonoacetate → HCID 57706483, compound

To a solution of 2-cyclopropylethanol (20.72 g, 240.6 mmol) (commercially available from Alfa Aesar) in 5:1 ACN/DCM (480 mL) were added TEMPO (1.879 g, 12.03 mmol) (commercially available from Aldrich) and iodobenzene diacetate (81.36 g, 252.6 mmol) (commercially available from Aldrich) as solids. The resulting slurry was stirred overnight at room temperature to afford a homogeneous solution. The reaction mixture was used directly in the next step. To a suspension of lithium chloride (15.30 g, 360.9 mmol) in ACN (400 mL) were added methyl 2-(diethoxyphosphoryl)acetate (48.04 mL, 288.7 mmol) (commercially available from Aldrich) and DBU (115.1 mL, 769.9 mmol) (commercially available from Aldrich) at room temperature. The mixture was cooled to 0° C., and to it was added 2-cyclopropylacetaldehyde (20.24 g, 240.6 mmol) solution dropwise. The resulting cloudy mixture was warmed to room temperature and stirred overnight. The mixture was partitioned between water and EtOAc. The layers were separated, and the aqueous phase was extracted with additional EtOAc. The combined organics were washed with water and brine, dried (MgSO4), and concentrated. The crude product was purified by silica gel flash chromatography (0-10% EtOAc/hexane) to afford 89.A as a colorless liquid.

1. customto afford a homogeneous solution
2. temperatureThe mixture was cooled to 0° C.
3. temperatureThe resulting cloudy mixture was warmed to room temperature
4. stirringstirred overnight
5. customThe mixture was partitioned between water and EtOAc
6. customThe layers were separated
7. extractionthe aqueous phase was extracted with additional EtOAc
8. washThe combined organics were washed with water and brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated
11. customThe crude product was purified by silica gel flash chromatography (0-10% EtOAc/hexane)

ORD record

ord-74f1a1f6a59c4b7682f291b549d2480a

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030354B2