Formaldehyde → 3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-yn-1-ol

온도

-78 °C

To a solution of 3-(2,2-dibromovinyl)-5-phenyl-4-(trifluoromethyl)isoxazole (Preparation 62A, 0.496 g, 1.19 mmol) in THF (6.0 mL) at −78° C. was slowly added a 2.5 M solution of butyl lithium in hexane (1.05 mL, 2.61 mmol). The reaction mixture was stirred at −78° C. for 25 min. and then warmed to room temperature gently with a heat gun. Once at room temperature, paraformaldehyde (0.713 g, 23.74 mmol) was added, and the reaction mixture was stirred for 5 min. The mixture was diluted with ether, washed with water (2×), and washed with brine. The combined aqueous layers were extracted with ether, and the combined organics layers were dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash silica gel chromatography using a mixture of ethyl acetate in hexane (1%-5%-20%) to give 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-yn-1-ol (0.199 g, 0.745 mmol, 63% yield) as a yellowish-orange solid. The product had an HPLC ret. time=2.39 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=268.17.

1. temperaturewarmed to room temperature gently with a heat gun
2. stirringthe reaction mixture was stirred for 5 min
3. washwashed with water (2×)
4. washwashed with brine
5. extractionThe combined aqueous layers were extracted with ether
6. dry with materialthe combined organics layers were dried over anhydrous sodium sulfate
7. concentrationconcentrated
8. customThe residue was purified by flash silica gel chromatography
9. additiona mixture of ethyl acetate in hexane (1%-5%-20%)

ORD 기록

ord-0350e825937a46ab9012da0a389bfa98

출처 데이터셋

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09216972B2