Diiodomethane → Methyl 3-(cyclopropylmethyl)-4,5-dimethoxybenzoate

Temperature

23 °C

To stirred dichloromethane (10 mL) at 0° C. was added Et2Zn (1.0 M in hexane, 10.0 mL, 10 mmol, 2 eq.). The resulting solution was then treated with a solution of TFA (0.77 mL, 10 mmol) in CH2Cl2 (5.0 mL) added over the course of 3 min. After stirring for 20 min at 0° C. diiodomethane (0.80 mL, 10.0 mmol) in CH2Cl2 was added. After 20 min at 0° C., a solution of 3-allyl-4,5-dimethoxybenzoic acid methyl ester (Example 30, Step 1, 1.18 g, 5.0 mmol) in CH2Cl2 (5.0 mL) was added and the reaction was warmed to 23° C. After 50 min the reaction was quenched by addition of 0.1 N HCl (25 mL) and then diluted with hexanes (100 mL). The organic layer was separated, washed with saturated NaHCO3 (100 mL), H2O (100 mL), brine (100 mL) dried MgSO4 and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel using 20% EtOAc in hexanes as an eluent to furnish 3-cyclopropylmethyl-4,5-dimethoxybenzoic acid methyl ester (0.96 g, 80% yield).

1. additionadded over the course of 3 min
2. additionwas added
3. customAfter 50 min the reaction was quenched by addition of 0.1 N HCl (25 mL)
4. additiondiluted with hexanes (100 mL)
5. customThe organic layer was separated
6. washwashed with saturated NaHCO3 (100 mL), H2O (100 mL), brine (100 mL) dried MgSO4
7. concentrationconcentrated in vacuo
8. customThe crude product was purified by flash column chromatography on silica gel using 20% EtOAc in hexanes as an eluent

ORD record

ord-358f182182dd4d33a76062f4f319e2c6

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07691843B2