Triethylamine → (1R,2S)-2-(3,4-difluoro-benzylamino)-cyclopentanecarboxylic acid methyl ester

Temperature

25 °C

The crude (1R,2S)-2-amino-cyclopentanecarboxylic acid methyl ester hydrochloride (prepared as described in Example 11a, 0.54 mmol) was dissolved in tetrahydrofuran (6 mL). Magnesium sulfate (185 mg), triethylamine (80 μL, 0.57 mmol) and 3,4-difluoro-benzaldehyde (122 μL, 1.11 mmol) were added at 25° C. and the resulted mixture was stirred at 25° C. for 16 h. The solid was filtered off and the filtrate was concentrated in vacuo to give an oil. This oil was dissolved in methanol (10 mL) and sodium borohydride (42 mg, 1.11 mmol) was then added portionwise. The mixture was stirred at 25° C. for 1 h. Saturated aqueous sodium bicarbonate solution (2 mL), water (2 mL) and saturated aqueous brine solution (1 mL) were added. The mixture was extracted with ethyl acetate (3×10 mL) and the organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford the desired product, (1R,2S)-2-(3,4-difluoro-benzylamino)-cyclopentanecarboxylic acid methyl ester (126.1 mg, 0.469 mmol, 86.7% over two steps). This crude product was directly used in next step without further purification. LC-MS (ESI) calcd for C14H17F2NO2 269.1, found 270.1 [M+H+].

1. filtrationThe solid was filtered off
2. concentrationthe filtrate was concentrated in vacuo
3. customto give an oil
4. stirringThe mixture was stirred at 25° C. for 1 h
5. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
6. dry with materialthe organic layer was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-2e28e50ecd9148759f0f5611a48ee596

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582626B2