Potassium Carbonate → methyl (2R)-2-(4-chloropyrazol-1-yl)propanoate

4-Chloro-1H-pyrazole (668 mg, 6.51 mmol) was dissolved in ethyl acetate and (S)-methyl 2-(trifluoromethylsulfonyloxy)propanoate (1.538 g, 6.51 mmol) was added followed by potassium carbonate (2.70 g, 19.5 mmol) while stirring at room temperature. The reaction mixture was stirred for 18 h. The mixture was diluted with methyl tert-butyl ether (15 mL), filtered through Celite, and washed with a mixture of ethyl acetate:methyl tert-butyl ether (1:1, 15 mL×4). The filtrate was reduced in volume by approximately 30-40 mL then was washed with aqueous hydrochloric acid (0.1 M, 25 mL), water and brine (15 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated to afford (R)-methyl 2-(4-chloro-1H-pyrazol-1-yl)propanoate as an oil (1.02 g). 1H NMR (500 MHz, CDCl3) δ 1.77 (d, 3H), 3.76 (s, 3H), 5.05 (q, 1H), 7.46 (s, 1H), 7.54 (s, 1H); MS (EI+) (M+) 188; Chiral HPLC retention time: 3.11 min (Method: Chiralpak AD-H 0.46×25 cm, Mobile Phase: 95/5 CO2/methanol; Flow: 2.5 mL/min); 73.3% ee.

1. stirringThe reaction mixture was stirred for 18 h
2. filtrationfiltered through Celite
3. washwashed with a mixture of ethyl acetate:methyl tert-butyl ether (1:1, 15 mL×4)
4. washthen was washed with aqueous hydrochloric acid (0.1 M, 25 mL), water and brine (15 mL)
5. dry with materialThe organic phase was dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated

ORD record

ord-c3a1d4c25fc24b1eb0d151e3563ec6f0

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296745B2