methyl (2S)-2-amino-3-cyclopentylpropanoate

Conditions: temp:82.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). The crude reaction mixture concentrated in vacuo to remove the acetonitrile The remaining solution was then diluted with water (10 mL) extracted with ethyl acetate (3×20 mL) the combined organics were then dried over magnesium sulfate filtered to remove the drying agent the filtrate concentrated in vacuo The residue was then purified

Conditions: temp:82.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). The crude reaction mixture concentrated in vacuo to remove the acetonitrile The remaining solution was then diluted with water (10 mL) extracted with ethyl acetate (3×20 mL) the combined organics were then dried over magnesium sulfate filtered to remove the drying agent the filtrate concentrated in vacuo The residue was then purified

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-Amino-3-cyclopentyl-propionic acid (Chemimpex, 1.0 g, 6.36 mmol), methanol (15 mL) and concentrated hydrochloric acid (2 mL) was placed in a reaction flask and heated at 65° C. for 16 h. After such time, the reaction mixture was concentrated in vacuo and then dissolved in water. The resulting solution was then treated with a saturated aqueous sodium bicarbonate solution until pH ˜7-9. It was then extracted with ethyl acetate and the organic layers combined, dried over magnesium sulfate, filtered to remove the drying agent and the filtrate concentrated in vacuo to afford (S)-2-amino-3-cyclopentyl-propionic acid methyl ester (796 mg, 73%) as a clear colorless oil: HR-ES(+) m/e calcd for C9H17NO2 [M+H]+ 172.1332, observed 172.1332; 1H NMR (300 MHz, DMSO-d6) δ ppm 3.60 (s, 3H), 3.25 (dd, J=6.04, 7.85 Hz, 1H), 1.34-1.96 (m, 9H), 0.92-1.14 (m, 2H). After such time, the reaction mixture was concentrated in vacuo dissolved in water The resulting solution was then treated with a saturated aqueous sodium bicarbonate solution until pH ˜7-9 It was then extracted with ethyl acetate dried over magnesium sulfate filtered to remove the drying agent the filtrate concentrated in vacuo

Conditions: temp:82.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). The crude reaction mixture concentrated in vacuo to remove the acetonitrile The remaining solution was then diluted with water (10 mL) extracted with ethyl acetate (3×20 mL) the combined organics were then dried over magnesium sulfate filtered to remove the drying agent the filtrate concentrated in vacuo The residue was then purified

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-Amino-3-cyclopentyl-propionic acid (Chemimpex, 1.0 g, 6.36 mmol), methanol (15 mL) and concentrated hydrochloric acid (2 mL) was placed in a reaction flask and heated at 65° C. for 16 h. After such time, the reaction mixture was concentrated in vacuo and then dissolved in water. The resulting solution was then treated with a saturated aqueous sodium bicarbonate solution until pH ˜7-9. It was then extracted with ethyl acetate and the organic layers combined, dried over magnesium sulfate, filtered to remove the drying agent and the filtrate concentrated in vacuo to afford (S)-2-amino-3-cyclopentyl-propionic acid methyl ester (796 mg, 73%) as a clear colorless oil: HR-ES(+) m/e calcd for C9H17NO2 [M+H]+ 172.1332, observed 172.1332; 1H NMR (300 MHz, DMSO-d6) δ ppm 3.60 (s, 3H), 3.25 (dd, J=6.04, 7.85 Hz, 1H), 1.34-1.96 (m, 9H), 0.92-1.14 (m, 2H). After such time, the reaction mixture was concentrated in vacuo dissolved in water The resulting solution was then treated with a saturated aqueous sodium bicarbonate solution until pH ˜7-9 It was then extracted with ethyl acetate dried over magnesium sulfate filtered to remove the drying agent the filtrate concentrated in vacuo