Acetonitrile → 3-(3-Bromophenyl)-3-hydroxypropanenitrile

Temperature

-50 °C

To a stirred mixture of THF (200 mL) and CH3CN (7.8 mL, 148 mmol) cooled to −50° C., was added KOtBu (18.16 g, 162 mmol) in portions by maintaining the temperature at −50° C. After stirring for 30 min, 3-bromobenzaldehyde (25 g, 135 mmol) was charged maintaining the same internal temperature. After stirring for 30 min, the reaction mixture was warmed to 0° C. and stirred for additional 3 h. This was recooled to −10° C. and quenched with excess water. Extraction with ethyl acetate yielded the crude product, which was purified by flash chromatography (0 to 20% EtOAc-hexanes gradient) to give 23 as light yellow oil. Yield (21 g, 69%): 1H NMR (400 MHz, DMSO-d6) δ 7.61 (s, 1H), 7.49 (bd, J=7.8 Hz, 1H), 7.47 (bd, J=7.6 Hz, 1H), 7.34 (t, J=7.6 Hz, 1H), 6.09 (d, J=4.4 Hz, 1H), 4.92 (m, 1H), 2.81-2.95 (m, 2H).

1. temperatureby maintaining the temperature at −50° C
2. temperaturemaintaining the same internal temperature
3. stirringAfter stirring for 30 min
4. temperaturethe reaction mixture was warmed to 0° C.
5. stirringstirred for additional 3 h
6. customThis was recooled to −10° C.
7. customquenched with excess water
8. extractionExtraction with ethyl acetate
9. customyielded the crude product, which
10. customwas purified by flash chromatography (0 to 20% EtOAc-hexanes gradient)

ORD record

ord-bd179ddeeaa04a228c6ae17de9d763f6

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08766007B2