Hydrochloric Acid → 1-[5-(6-Ethoxy-2-methylsulfanyl-pyrimidin-4-yl)-thiophen-2-yl]-4,4,4-trifluoro-butane-1,3-dione

온도

-78 °C

1-[5-(6-Ethoxy-2-methylsulfanyl-pyrimidin-4-yl)-thiophen-2-yl]-ethanone (210 mg, 0.71 mmol) was dissolved in anhydrous THF (7 mL) and cooled to −78° C. under nitrogen atmosphere. A solution of lithium bis(trimethylsilyl)amide (0.71 mL, 1.0 M) in THF was added. The reaction mixture was stirred at −20° C. under nitrogen atmosphere for 1 h. The reaction mixture was then cooled to −78° C. To this reaction mixture was added ethyl trifluoroacetate (170 μL, 1.43 mmol). The vigorously stirred solution was allowed to warm to ambient temperature overnight. The reaction mixture was poured into 20 mL of ice and water and was brought to pH=3˜4 by adding 10% HCl aqueous solution. The mixture was then extracted with diethyl ether (20 mL×3) three times. The ether layer was separated and dried with anhydrous MgSO4 and concentrated in vacuo to give crude product 1-[5-(6-ethoxy-2-methylsulfanyl-pyrimidin-4-yl)-thiophen-2-yl]-4,4,4-trifluoro-butane-1,3-dione (272 mg, 98% yield). 1H-NMR (CDCl3): δ 7.81 (m, 1 H), 7.68 (m, 1 H), 6.70 (s, 1 H), 6.47 (s, 1 H), 4.47 (q, J=7.1 Hz, 2 H), 2.61 (s, 3 H), 1.41 (t, J=7.1 Hz, 3 H).

1. temperatureThe reaction mixture was then cooled to −78° C
2. temperatureto warm to ambient temperature overnight
3. extractionThe mixture was then extracted with diethyl ether (20 mL×3) three times
4. customThe ether layer was separated
5. dry with materialdried with anhydrous MgSO4
6. concentrationconcentrated in vacuo

ORD 기록

ord-d61f4e7f48754d5e9b51be3360c4509c

출처 데이터셋

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07482366B2