4-Hydroxybenzaldehyde → Tert-butyl 2-(4-formylphenoxy)acetate

Temperature

0 °C

A suspension of NaH (60% in mineral oil, 3.69 g, 92.2 mmol) in dry DMF (70 ml) was cooled to 0° C. A solution of 4-hydroxybenzaldehyde (10.0 g, 82.0 mmol) in dry DMF (35 ml) was added dropwise. The mixture was stirred at 0° C. for 40 minutes. tert-Butyl bromoacetate (12.1 ml, 82.5 mmol) was added and the mixture was stirred at room temperature for 17 h. The mixture was concentrated under reduced pressure. Diethyl ether was added and the mixture was washed with 10% NH4Cl, water and brine. The organic phase was dried (MgSO4), concentrated under reduced pressure and purified by flash-chromatography (10%-20% EtOAc in hexane). This gave tert-butyl (4-formylphenoxy)acetate (17.4 g, 73.4 mmol, 90% yield) as an colourless oil. This intermediate was dissolved in dry toluene (120 ml) and 4-chloroaniline (9.37 g, 73.4 mmol) was added. The mixture was refluxed in a Dean-Stark apparatus for 20 h, cooled and concentrated under reduced pressure. Hexane was added and the formed precipitate was filtered, washed twice with cold hexane and dried. This afforded 20.0 g (79%) of the title compound as a yellow solid. 1H-NMR (CDCl3, 200 MHz): δ 1.5 (s, 9H), 4.6 (s, 2H), 7.0 (d, 2H), 7.2 (d, 2H), 7.4 (d, 2H), 7.8 (d, 2H), 8.4 (s, 1H). MS (CI) M/z: 368.0 (M++Na, 100), 369.0 (20), 370.0 (30), 371.0 (10).

1. stirringthe mixture was stirred at room temperature for 17 h
2. concentrationThe mixture was concentrated under reduced pressure
3. additionDiethyl ether was added
4. washthe mixture was washed with 10% NH4Cl, water and brine
5. dry with materialThe organic phase was dried (MgSO4)
6. concentrationconcentrated under reduced pressure
7. custompurified by flash-chromatography (10%-20% EtOAc in hexane)

ORD record

ord-444d020cfa854d8dbda265bfc12cc6f5

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07871998B2