Methyl chloroformate → 4-Cyclopropyl-2-ethyl-5-(methoxycarbonyl)benzoic acid

Temperature

-78 °C

To a solution of 4-cyclopropyl-2-ethyl-5-iodobenzoic acid (compound 226.5, 500 mg, 1.58 mmol, 1.00 equiv) in THF/Et2O (10/10 mL) under nitrogen at −78° C. was added dropwise n-butyllithium (2.5 M, 1.88 mL, 3.00 equiv) over 3 min. After stirring for 10 min at −78° C., methyl chloroformate (230 mg, 2.43 mmol, 1.50 equiv) was added dropwise at −78° C. The resulting solution was stirred for 40 min at −78° C., then warmed slowly to −35° C. The reaction was carefully quenched with 2 mL of water. The pH was adjusted to ˜4-5 with hydrogen chloride (aq., 1 M). The resulting mixture was extracted with 3×20 mL of ethyl acetate and the combined organic layers were dried (Na2SO4) and concentrated under reduced pressure to yield 400 mg the title compound as a yellow solid.

1. stirringThe resulting solution was stirred for 40 min at −78° C.
2. temperaturewarmed slowly to −35° C
3. customThe reaction was carefully quenched with 2 mL of water
4. extractionThe resulting mixture was extracted with 3×20 mL of ethyl acetate
5. dry with materialthe combined organic layers were dried (Na2SO4)
6. concentrationconcentrated under reduced pressure

ORD record

ord-747570201f1e4814bc98ef12ae9968ee

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2