Acetonitrile → (S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester

Temperature

82 °C

A mixture of 2-bromomethyl-3-trifluoromethyl-benzoic acid methyl ester (695 mg, 2.34 mmol), (S)-2-amino-3-cyclopentyl-propionic acid methyl ester (400 mg, 2.34 mmol), triethylamine (358 μL, 2.57 mmol), and acetonitrile (20 mL) was heated at 82° C. for 7 h. The crude reaction mixture was treated with water (5 mL) and then concentrated in vacuo to remove the acetonitrile. The remaining solution was then diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL), the combined organics were then dried over magnesium sulfate, filtered to remove the drying agent and the filtrate concentrated in vacuo. The residue was then purified via automated flash chromatography (12 g silica gel column, 10-40% ethyl acetate/hexanes) to afford (S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester (675 mg, 81%) as a clear colorless oil: [α]25D=−16.0°, (c=0.15, methylene chloride); HR-ES(+) m/e calcd for C18H20NO3F3 [M+H]+ 356.1468, observed 356.1466; 1H NMR (300 MHz, DMSO-d6, ppm) δ 8.02 (t, J=8.00 Hz, 2H), 7.71-7.89 (m, 1H), 4.92 (dd, J=4.08, 10.41 Hz, 1H), 4.69 (s, 2H), 3.66 (s, 3H), 0.94-2.21 (m, 11H).

1. customThe crude reaction mixture
2. concentrationconcentrated in vacuo
3. customto remove the acetonitrile
4. additionThe remaining solution was then diluted with water (10 mL)
5. extractionextracted with ethyl acetate (3×20 mL)
6. dry with materialthe combined organics were then dried over magnesium sulfate
7. filtrationfiltered
8. customto remove the drying agent
9. concentrationthe filtrate concentrated in vacuo
10. customThe residue was then purified

ORD record

ord-e16b7a5a654f437bba8c61a50c72d98e

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697705B2