Pivalaldehyde → racemic (R/S)-1-(5-methoxy-2-nitrophenyl)-2,2-dimethyl-1-propanol

Temperature

40 °C

To a solution of 3-iodo-4-nitroanisole (2.79 g, 10.0 mmol) in anhydrous THF (10 mL) at minus 40° C. under a nitrogen atmosphere, phenylmagnesium chloride (2 M in THF, 4.2 mL, 8.3 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 two hours, followed by addition of trimethylacetaldehyde (1.1 mL, 10 mmol). The mixture was stirred at minus 40° C. for two hours and then at room temperature for another one hour. The reaction was then quenched with brine (100 mL), and the mixture was extracted with CH2Cl2 (40 mL) three times. The combined organic phase was dried over Na2SO4, concentrated in vacuo, and the residue was purified by silica gel column chromatography to yield racemic (R/S)-1-(5-methoxy-2-nitrophenyl)-2,2-dimethyl-1-propanol (1.76 g, 88%). 1H NMR (400 MHz, CDCl3): δ 7.89 (d, 1H, J=9.2 Hz, Ph-H), 7.27 (d, 1H, J=2.8 Hz, Ph-H), 6.84 (dd, 1H, J=8.8 and 2.8 Hz, Ph-H), 5.62 (d, 1H, J=4.0 Hz, PhCH), 3.89 (s, 3H, OCH3), 2.08 (d, 1H, J=4.0 Hz, OH), 0.89 (s, 9H, C(CH3)3).

1. customexceed minus 35° C
2. additionUpon completion of the addition
3. stirringThe mixture was stirred at minus 40° C. for two hours
4. waitat room temperature for another one hour
5. customThe reaction was then quenched with brine (100 mL)
6. extractionthe mixture was extracted with CH2Cl2 (40 mL) three times
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-f2e38a7a3ef64f899018ed0eae1bdb49

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889860B2