2-Nitro-4-(trifluoromethyl)phenol

2-Nitro-4-trifluoromethyl-phenol (2.07 g, 10 mmol), 1-methyl-piperidin-4-ol (1.21 g, 10.5mmol), and triphenylphosphine (2.75 g, 10.5 mmol)were diluted with 30 mL of THF and placed undernitrogen. 'The reaction mixture was cooled to 0C, then DIAD (2.12 g, 10.5 mmol) in 1 mL of THF wasadded dropwise. The reaction mixture was allowed tostir for 12 hours warming to room temperature. Thereaction was diluted with ethyl acetate (150 mL) andsodium carbonate (150 mL of a 10% aq. solution).The organic layer was washed with brine, dried overMgSO4, filtered, and dried under reduced pressure.The product was purified using a Biotage 40M car- tridge, eluting with hexane/ethyl acetate (500 mL1/1), then CH2Cl2/MeOH/NH4OH (98/8/2, 500 mL) toyield a light yellow oil.(a) 2-Nitro-4-trifluoromethylphenol Powdered sodium hydroxide (48 g) was added in portions over a period of 24 hours to a stirred solution of 4-chloro-3-nitrobenzotrifluoride (90 g) in dimethylsulfoxide (120 ml). After stirring the mixture vigorously for a further day another portion of powdered sodium hydroxide (4.8 g) was added and stirring was continued for a further 8 hours period. The mixture was poured into cold water (1 litre) and extracted with diethyl ether. The aqueous phase was acidified with concentrated hydrochloric acid, extracted with diethyl ether and the ethereal phase was washed with brine. The washed ethereal solution was dried over anhydrous magnesium sulfate and the solvent was evaporated to give the title compound as a brown oil (50 g).EXAMPLE 6 6-(trifluoromethyl)-3, 4-dihydro-N-(2-propenyl)-2H-1, 4-benzoxazine-2-carboxamide (6) 87.6 g of finely powdered sodium hydroxide was added in portions over an 8-hour period to a stirred solution of 165.0 g of 2-nitro-4-(trifluoromethyl)chlorobenzene in 220 ml of dimethyl sulfoxide at room temperature. The mixture was allowed to stand overnight, then poured into 1.5 liters of cold water. The resulting mixture was acidified to pH 1 with concentrated hydrochloric acid. An oil formed; it was separated and dissolved in ether. The solution was dried (MgSO4) and stripped of solvent under reduced pressure. The residue was mixed with cold sodium hydroxide solution and the mixture was extracted with petroleum ether. The water layer was acidified with concentrated hydrochloric acid. The resulting oil was separated and dissolved in ether. The solution was dried (MgSO4) and stripped of solvent to give EXAMPLE 7 ethyl 6-(trifluoromethyl)-3, 4-dihydro-2H-1, 4-benzoxazine-2-carboxylate (7) 87.6 g of finely powdered sodium hydroxide was added in portions over an 8-hour period to a stirred solution of 164.0 g of 2-nitro-4-(trifluoromethyl)chlorobenzene in 200 ml of dimethyl sulfoxide at room temperature. The mixture was allowed to stand overnight, then poured into 1.5 liters of cold water. The resulting mixture was acidified to pH 1 with concentrated hydrochloric acid. An oil formed; it was separated and dissolved in ether. The solution was dried (MgSO4) and stripped of solvent under reduced pressure. The residue was mixed with cold sodium hydroxide solution and the mixture was extracted with petroleum ether. The water layer was acidified with concentrated hydrochloric acid and the resulting oil was separated and dissolved in ether. The solution was dried (MgSO4) and stripped of solvent to give EXAMPLE 10 45 g of 4-chloro-3-nitro-benzotrifluoride, dissolved in 150 ml of methanol, are initially introduced. 80 g of an ion exchanger resin containing quaternary ammonium groups are then introduced, the mixture is stirred for 10 minutes, 100 g of 50% strength sodium hydroxide solution are added dropwise, up to a maximum temperature of 70 C., and the mixture is stirred at 65 C. for 8 hours. After cooling the mixture, it is acidified with concentrated hydrochloric acid, the ion exchanger is filtered off and the crude product is distilled with steam. 27 g of A) General procedure: DBU (31 mul, 0.21 mmol) and DPPA (47 mul, 0.22 mmol) were added to the phenol solution (0.20 mmol) in toluene (1.0 mL). After stirring for 0.25-16 h at rt or reflux, the mixture was diluted with AcOEt (30 mL). Next, the mixture was washed with saturated aqueous NaHCO3 (25 mL) and brine (25 mL) before being dried over Na2SO4. Concentration of the solvent in vacuo, followed by purification of the residue on a silica gel column (AcOEt:n-hexane 1:1-1:20), gave the desired aryl azide.

Molecular Weight:207.11
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Exact Mass:207.01432748
Monoisotopic Mass:207.01432748
Topological Polar Surface Area:66
Heavy Atom Count:14
Complexity:225
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes