Trimethylsilyldiazomethane → Methyl 4-isobutyl-3-(trifluoromethyl)benzoate

To 4-isobutyl-3-(trifluoromethyl)benzoic acid (Preparation 23A, 0.55 g, 2.234 mmol) in dichloromethane (5 mL) and methanol (2.00 mL) was added trimethylsilyldiazomethane (1.452 mL, 2.90 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 30 min. Excess trimethylsilyldiazomethane was quenched by the slow addition of acetic acid (˜0.5 ml) at room temperature. The reaction mixture was concentrated and partitioned between ethyl acetate (20 mL) and sat. aq. sodium bicarbonate (10 mL). The ether layer was washed with brine (10 mL), dried over sodium sulfate, and concentrated. The resulting dark oil was subjected to silica gel column chromatography (hexane/ethyl acetate). Fractions corresponding to the product were collected and concentrated to yield an oil. The oil was azeotroped with THF (2×5 mL) and dried under high vacuum to yield methyl 4-isobutyl-3-(trifluoromethyl)benzoate (0.52 g, 1.998 mmol, 89% yield) as a clear liquid.

1. customExcess trimethylsilyldiazomethane was quenched by the slow addition of acetic acid (˜0.5 ml) at room temperature
2. concentrationThe reaction mixture was concentrated
3. custompartitioned between ethyl acetate (20 mL) and sat. aq. sodium bicarbonate (10 mL)
4. washThe ether layer was washed with brine (10 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated
7. customFractions corresponding to the product were collected
8. concentrationconcentrated
9. customto yield an oil
10. customThe oil was azeotroped with THF (2×5 mL)
11. customdried under high vacuum

ORD record

ord-b2dde122069b4bd0affc1f1caa8af38f

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216972B2