Isobutyraldehyde → (R/S)-1-(4-methoxy-2-nitrophenyl)-2-methyl-1-propanol

To a solution of 4-iodo-3-nitroanisole (2.79 g, 10.0 mmol) in anhydrous THF (20 mL) at minus 40° C. under a nitrogen atmosphere, phenylmagnesium chloride (2 M in THF, 6.0 mL, 12 mmol) was added dropwise at a rate such that the temperature would not exceed minus 35° C. Upon completion of the addition, the mixture was stirred at minus 40° C. for five min, followed by addition of isobutyraldehyde (1.8 mL, 20 mmol). The mixture was gradually warmed to room temperature, quenched with saturated NH4Cl solution (5.0 mL), diluted with CH2Cl2 (100 mL) and washed with water (100 mL). The organic phase was separated, and the aqueous phase was extracted with CH2Cl2 (50 mL) three times. The combined organic phase was washed with brine (40 mL), dried over Na2SO4, concentrated in vacuo, and the residue was purified by silica gel column chromatography to yield (R/S)-1-(4-methoxy-2-nitrophenyl)-2-methyl-1-propanol (1.5 g, 67%) as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.61 (d, 1H, J=8.8 Hz, Ph-H), 7.34 (d, 1H, J=2.8 Hz, Ph-H), 7.15 (dd, 1H, J=8.8 and 2.8 Hz, Ph-H), 4.92 (dd, 1H, J=5.6 and 3.2 Hz, Ph-CH), 2.46 (br s, 1H, OH), 2.00 (m, 1H, CH), 0.97 (d, 3H, J=6.4 Hz, CH3), 0.86 (d, 3H, J=6.8 Hz, CH3).

1. customexceed minus 35° C
2. additionUpon completion of the addition
3. temperatureThe mixture was gradually warmed to room temperature
4. customquenched with saturated NH4Cl solution (5.0 mL)
5. additiondiluted with CH2Cl2 (100 mL)
6. washwashed with water (100 mL)
7. customThe organic phase was separated
8. extractionthe aqueous phase was extracted with CH2Cl2 (50 mL) three times
9. washThe combined organic phase was washed with brine (40 mL)
10. dry with materialdried over Na2SO4
11. concentrationconcentrated in vacuo
12. customthe residue was purified by silica gel column chromatography

ORD record

ord-25783c46c34846e4aa33a5192c22af5e

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889860B2