Ethanol → Ethyl 4-(2-hydroxy-2-methyl-propoxy)-3-methyl-benzoate

Temperature

80 °C

A mixture of 1-chloro-2-methyl-propan-2-ol (10 mL), 4-hydroxy-3-methyl-benzoic acid (2.0 g, 13.15 mmol), potassium carbonate (7.3 g, 52.71 mmol), water (6 mL) and ethanol (60 mL) was heated at 80° C. for 16 hours. The reaction mixture was cooled to room temperature and partitioned between 1N NaOH and EtOAc and the layers were separated. The organic layer was washed with 1N NaOH (2×10 mL) and the combined aqueous layers were washed with EtOAc. The combined organic layers were dried and concentrated in vacuo to give ethyl 4-(2-hydroxy-2-methyl-propoxy)-3-methyl-benzoate. The ester was dissolved in ethanol (15 mL) and water (2 mL), sodium hydroxide (1.1 g, 26.30 mmol) was added and the reaction mixture was stirred at 40° C. for 4 hours. The reaction mixture was poured into 1N NaOH solution and extracted with ether (2×10 mL). The aqueous layer was acidified to pH 2-3 using 6N HCl solution and extracted with EtOAc (3×10 mL). The organics were separated and washed with brine solution. The organic layer was dried (Na2SO4) and concentrated in vacuo and the resulting material was triturated with ether to give 4-(2-hydroxy-2-methyl-propoxy)-3-methyl-benzoic acid (2.2 g, 75%) as a white solid. ESI-MS m/z calc. 224.1. Found 225.5 (M+1); Retention time: 1.06 minutes (3 min run) 1H NMR (400 MHz, DMSO) δ 7.75 (dd, J=8.5, 2.0 Hz, 1H), 7.73-7.70 (m, 1H), 6.96 (d, J=8.6 Hz, 1H), 4.67 (s, 1H, OH), 3.76 (s, 2H), 2.20 (s, 3H), 1.22 (s, 6H).

1. temperatureThe reaction mixture was cooled to room temperature
2. custompartitioned between 1N NaOH and EtOAc
3. customthe layers were separated
4. washThe organic layer was washed with 1N NaOH (2×10 mL)
5. washthe combined aqueous layers were washed with EtOAc
6. customThe combined organic layers were dried
7. concentrationconcentrated in vacuo

ORD record

ord-54ee4bea12a5467488259e72de207ea6

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08828996B2