Pivalaldehyde → 1-(2-Nitrophenyl)-2,2-dimethyl-1-propanol

Temperature

40 °C

Under a nitrogen atmosphere, a solution of 1-iodo-2-nitrobenzene (3.0 g, 12 mmol) in anhydrous THF (30 mL) was cooled to minus 40° C., and then phenylmagnesium chloride (2 M in THF, 7.2 mL, 14.5 mmol) was added dropwise at a rate that the temperature would not exceed minus 35° C. After the mixture was stirred for 20 minutes at minus 40° C., trimethylacetaldehyde (1.85 mL, 16.8 mmol) was added dropwise and the mixture was stirred for another 30 minutes at minus 40° C. The mixture was gradually warmed up to room temperature, quenched with saturated ammonium chloride (60 mL), poured into water (60 mL), and extracted with ethyl acetate three times (60 mL each). The combined organic phase was dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography to yield (RS)-1-(2-nitrophenyl)-2,2-dimethyl-1-propanol (1.82 g, 72%) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 7.82 (d, 1H, J=6.4 Hz, Ph-H), 7.76 (d, 1H, J=6.4 Hz, Ph-H), 7.61 (t, 1H, J=6.4 Hz, Ph-H), 7.39 (t, 1H, J=6.4 Hz, Ph-H), 5.39 (d, 1H, J=2.8 Hz, Ph-CH), 2.14 (d, 1H, J=3.2 Hz, OH), 0.89 (s, 9H, C(CH3)3).

1. customexceed minus 35° C
2. additionwas added dropwise
3. temperatureThe mixture was gradually warmed up to room temperature
4. customquenched with saturated ammonium chloride (60 mL)
5. additionpoured into water (60 mL)
6. extractionextracted with ethyl acetate three times (60 mL each)
7. dry with materialThe combined organic phase was dried over Na2SO4
8. concentrationconcentrated in vacuo
9. customThe residue was purified by silica gel column chromatography

ORD record

ord-54b2d13290d840ebaccae9995de7fb4b

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08877905B2