Isopropanol → HCID 58404446, compound

Under an atmosphere of nitrogen a mixture of 4-hydroxy-3-(trifluoromethyl)benzonitrile (5.89 g, 31.5 mmol) and triphenylphosphine (13.21 g, 50.4 mmol) in anhydrous THF (200 mL) was stirred for 5 min. at ambient temperature. To the solution DBAD (11.60 g, 50.4 mmol) was added, stirred 5 min before the addition of 2-propanol (3.03 mL, 39.3 mmol). The mixture was stirred at ambient temperature for 72 hr. The solvent was removed under reduced pressure. The resulting oil was triturated with 30-60° C. pet/ether (200 mL), filtered to remove phosphine oxide and the crude product was purified further by elution through silica with heptane/ethyl acetate (4:1). The isolated oil was dissolved in dichloromethane (200 mL) and stirred with TFA (4.85 mL, 63.0 mmol) for 90 min. at ambient temperature. The solution was basified with 2.5N NaOH (30 mL) and the product was partitioned between DCM and the basic aqueous phase to give the crude 4-isopropoxy-3-(trifluoromethyl)benzonitrile (6.56, 91%). LCMS (Table 1, Method a) Rt=2.32 min, 1H NMR (400 MHz, CDCl3) 7.85 (d, 1H), 7.75 (dd, 1H), 7.06 (d, 1H), 4.73 (m, 1H), 1.41 (dd, 6H).

1. stirringThe mixture was stirred at ambient temperature for 72 hr
2. customThe solvent was removed under reduced pressure
3. customThe resulting oil was triturated with 30-60° C. pet/ether (200 mL)
4. filtrationfiltered
5. customto remove phosphine oxide
6. customthe crude product was purified further by elution through silica with heptane/ethyl acetate (4:1)
7. dissolutionThe isolated oil was dissolved in dichloromethane (200 mL)
8. customthe product was partitioned between DCM

ORD record

ord-257fad24124e428d886cdc5e86117308

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834039B2