Chloroiodomethane → [2-(Cyclopropyloxy)phenyl]acetic acid

Temperature

0 °C

Diethyl zinc (2.34 mL, 2.34 mmol, 1M in heptane) was cooled to 0° C. under nitrogen then chloroiodomethane (0.35 mL, 4.68 mmol) in DCE (1 mL) was added drop-wise. The mixture was stirred under nitrogen at 0° C. for 20 minutes then methyl[2-(vinyloxy)phenyl]acetate (Preparation 156, 150 mg, 0.78 mmol) in DCE (1 mL) was added. The reaction mixture was stirred at 00° C. for 30 minutes then stirred at room temperature for 17 hours. Saturated aqueous ammonium chloride (10 mL) was added and the mixture was extracted with DCM (4×8 mL). The combined organic phases were dried over magnesium sulphate and evaporated in vacuo. Sodium hydroxide (3.28 mL, 3.28 mmol, 1 M) was added to the residue in THF (3 mL). The mixture was heated at 80° C. for 17 hours then evaporated in vacuo. Hydrochloric acid (10 mL, 1 M) was added to the residue then extracted with EtOAc (10 mL). The organic phase was evaporated in vacuo to afford the title compound as a yellow oil in 53% yield, 83 mg.

1. stirringThe reaction mixture was stirred at 00° C
2. stirringfor 30 minutes then stirred at room temperature for 17 hours
3. extractionthe mixture was extracted with DCM (4×8 mL)
4. dry with materialThe combined organic phases were dried over magnesium sulphate
5. customevaporated in vacuo
6. temperatureThe mixture was heated at 80° C. for 17 hours
7. customthen evaporated in vacuo
8. additionHydrochloric acid (10 mL, 1 M) was added to the residue
9. extractionthen extracted with EtOAc (10 mL)
10. customThe organic phase was evaporated in vacuo

ORD record

ord-d23a508fe3c54a0fbed9fa92d3f6fa77

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846698B2