1-[5-(Methoxymethyl)isoxazol-3-yl]ethanone → 2-[5-(Methoxymethyl)isoxazol-3-yl]but-3-yn-2-ol

To a solution of 1-[5-(methoxymethyl)isoxazol-3-yl]ethanone (220 mg, 1.42 mmol) in dry THF (4 mL) at 0° C. under an atmosphere of nitrogen, was introduced ethynylmagnesium bromide (4.4 mL of a 0.5M solution in THF, 2.20 mmol) dropwise over 5 min. After 1.5 hr at this temperature, the reaction was carefully quenched with water (0.2 mL) and the resulting suspension concentrated in vacuo. The residual syrup was slurried in water (5 mL) and the pH adjusted to 2 with 5M aqueous hydrochloric acid for 5 min., then saturated sodium bicarbonate solution introduced until the pH was ˜7.5. Following extraction of the basic aqueous solution with EtOAc (2×100 ml), the combined EtOAc extracts were dried (Na2SO4), filtered and the filtrate concentrated in vacuo to furnish the crude title compound as a pale brown oil: 1H NMR (500 MHz, CDCl3) delta 1.89 (3H, s), 2.66 (1H, s), 3.02 (1H, br. s), 3.45 (3H, s), 4.55 (2H, s), 6.39 (1H, s); LC-MS: m/z=+181.95 (M+H)+.

1. customthe reaction was carefully quenched with water (0.2 mL)
2. concentrationthe resulting suspension concentrated in vacuo
3. waitthe pH adjusted to 2 with 5M aqueous hydrochloric acid for 5 min.
4. additionsaturated sodium bicarbonate solution introduced until the pH was ˜7.5
5. extractionextraction of the basic aqueous solution with EtOAc (2×100 ml)
6. dry with materialthe combined EtOAc extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationthe filtrate concentrated in vacuo

ORD record

ord-0f105b49812a41aeba19f07611842999

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901313B2