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

Temperatur

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-Eintrag

ord-4eb1f8f066aa48d090ddd8db3a659056

Quelldatensatz

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08470866B2