Citric Acid → 5-(3,3,3-trifluoropropyl)-1H-pyrrole-2-carboxylic acid

2-(3,3,3-Trifluoro-propyl)-1H-pyrrole (8.15 mmol, 1.33 g) was added to a solution of trichloroacetyl chloride (8.15 mmol, 0.91 ml) in diethyl ether (10 ml). The resulting solution was held at room temperature for 1 h, then concentrated under reduced pressure. The resulting solid was dissolved in 1:1 dioxane-water (20 ml), treated with lithium hydroxide (24.5 mmol, 0.59 g), and heated to reflux for 30 minutes. After cooling to room temperature, the solution was acidified with saturated aqueous citric acid (20 ml), then extracted with ethyl acetate (2×50 ml). The combined organics were concentrated under reduced pressure. Purification of the resulting solid by silica gel chromatography provided 1.15 g (68%) of 5-(3,3,3-trifluoropropyl)-1H-pyrrole-2-carboxylic acid. 1H NMR (CDCl3) δ 9.33 (1H, br s), 6.99 (1H, dd, J=3.7, 2.5), 6.07 (1H, t, J=3.3), 2.96-2.89 (2H, m), 2.55-2.39 (2H, m).

1. concentrationconcentrated under reduced pressure
2. dissolutionThe resulting solid was dissolved in 1:1 dioxane-water (20 ml)
3. temperatureheated
4. temperatureto reflux for 30 minutes
5. extractionextracted with ethyl acetate (2×50 ml)
6. concentrationThe combined organics were concentrated under reduced pressure
7. customPurification of the resulting solid by silica gel chromatography

ORD record

ord-ebb72d5e5e6f47d4a96e4a2c25f1f4e5

Source dataset

uspto-grants-2005_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06872745B2