Isobutyraldehyde → 2-Methyl-1-(2-nitrophenyl)propan-1-ol

Temperature

40 °C

To a solution of 1-iodo-2-nitrobenzene (1.12 g, 4.5 mmol) in anhydrous THF (15 mL) cooled to minus 40° C. under nitrogen atmosphere, a solution of phenylmagnesium chloride (2 M in THF, 2.4 mL, 4.8 mmol) was added dropwise at a rate that the temperature would not exceed minus 35° C. Upon completion of the addition the mixture was stirred for five minutes at minus 40° C., followed by addition of isobutyraldehyde (0.545 mL, 6.0 mmol). The mixture was gradually warmed up to room temperature, quenched with saturated ammonium chloride (6 mL), poured into water (80 mL), and extracted with ethyl acetate three times (100 mL). Combined organic phase was washed with brine (80 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography to yield racemic (RS)-1-(2-nitrophenyl)-2-methyl-propanol (0.876 g, 99%) as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.84 (dd, 1 H, J=1.2 and 8.2 Hz, Ph-H), 7.73 (dd, 1 H, J=1.4 and 7.9 Hz, Ph-H), 7.61 (m, 1 H, Ph-H), 7.39 (m, 1 H, Ph-H), 5.03 (dd, 1 H, J=4.5 and 5.8 Hz, Ph-CH), 2.42 (d, 1 H, J=4.5 Hz, OH), 2.02 (m, 1 H, CH), 0.95 (d, 3 H, J=6.7 Hz, CH3), 0.89 (d, 3 H, J=6.8 Hz, CH3); 13C NMR (100 MHz, CDCl3): δ 148.48 (C), 138.91 (C), 132.95 (CH), 128.85 (CH), 127.95 (CH), 124.21 (CH), 73.79 (CH), 34.30 (CH), 19.66 (CH3), 17.01 (CH3).

1. customexceed minus 35° C
2. additionUpon completion of the addition the mixture
3. temperatureThe mixture was gradually warmed up to room temperature
4. customquenched with saturated ammonium chloride (6 mL)
5. additionpoured into water (80 mL)
6. extractionextracted with ethyl acetate three times (100 mL)
7. washCombined organic phase was washed with brine (80 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo
10. customThe residue was purified by silica gel column chromatography

ORD record

ord-9d9245d5b687459aa20b415385db3f79

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200319B2