tert-butyl N-[2-(4-hydroxyphenyl)ethyl]carbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(t-butoxycarbonyl)-2-(4-hydroxyphenyl)ethylamine (1.3 g) and 3,3,3-triphenylpropanol (1.4 g) were coupled by the method of example 5. The product (1.4 g) was dissolved in 15 mL isopropanol containing 1.0 g HCl, and stirred 3 hr at room temperature. A precipitate formed, which was collected and recrystallized from ethanol-ether to provide the hydrochloride salt of the title compound as a white solid, mp 163°-165° C., in 66% yield. Anal. calcd. for C29H29NO·HCl·0.75 H2O: C, 76.13; H, 6.94; N, 3.06. Found: C, 75.99; H, 6.81; N, 3.02. A precipitate formed which was collected recrystallized from ethanol-ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of potassium carbonate (K2CO3; 1.4 grams (g), 10.11 millimole (mmol)) in acetone (40 milliliters (mL)) was added bromomethylbenzene (1.73 g, 10.11 mmol) and tert-butyl 2-(4-hydroxyphenyl)ethylcarbamate (2 g, 8.4 mmol). The reaction mixture was heated at reflux for 15 hours (h) and then concentrated in vacuo. The residue was partitioned between diethyl ether (Et2O) and water (H2O), and the organic fraction was washed with brine, dried over sodium sulfate (Na2SO4), suction filtered, and concentrated in vacuo. The residue was purified by silica gel (SiO2) flash chromatography with 25% Et2O in hexane to afford [2-(4-benzyloxyphenyl)-ethyl]-carbamic acid tert-butyl ester as a white solid (2.4 g). This was dissolved in CH2Cl2 (50 mL) and trifluoroacetic acid (5 mL) was added. After stirring 16 h, the solvent was removed in vacuo, and the residue was redissolved in CH2Cl2, washed with 1M sodium hydroxide (NaOH), dried (Na2SO4) and filtered. The solvent was removed in vacuo to yield 2-(4-benzyloxyphenyl)-ethylamine (1.5 g). This was used without purification in the next step. The reaction mixture was heated at reflux for 15 hours (h) concentrated in vacuo The residue was partitioned between diethyl ether (Et2O) and water (H2O) the organic fraction was washed with brine dried over sodium sulfate (Na2SO4), suction filtered concentrated in vacuo The residue was purified by silica gel (SiO2) flash chromatography with 25% Et2O in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: t-Butyl [2-(4-hydroxyphenyl)ethyl]carbamate, benzyl bromoacetate and potassium carbonate were heated in acetone. t-Butyl [p-[[(benzyloxy)-carbonyl]methoxy]phenethyl]carbamate, MS: 385 (0.5, M), was obtained.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(t-butoxycarbonyl)-2-(4-hydroxyphenyl)ethylamine (1.3 g) and 3,3,3-triphenylpropanol (1.4 g) were coupled by the method of example 5. The product (1.4 g) was dissolved in 15 mL isopropanol containing 1.0 g HCl, and stirred 3 hr at room temperature. A precipitate formed, which was collected and recrystallized from ethanol-ether to provide the hydrochloride salt of the title compound as a white solid, mp 163°-165° C., in 66% yield. Anal. calcd. for C29H29NO.HCl.0.75 H2O: C, 76.13; H, 6.94; N, 3.06. Found: C, 75.99; H, 6.81; N, 3.02. A precipitate formed which was collected recrystallized from ethanol-ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(t-butoxycarbonyl)-2-(4-hydroxyphenyl)ethylamine (1.3 g) and 3,3,3-triphenylpropanol (1.4 g) were coupled by the method of example 5. The product (1.4 g) was dissolved in 15 mL isopropanol containing 1.0 g HCl, and stirred 3 hr at room temperature. A precipitate formed, which was collected and recrystallized from ethanol-ether to provide the hydrochloride salt of the title compound as a white solid, mp 163°-165° C., in 66% yield. Anal. calcd. for C29H29NO.HCl.0.75 H2O: C, 76.13; H, 6.94; N, 3.06. Found: C, 75.99; H, 6.81; N, 3.02. A precipitate formed which was collected recrystallized from ethanol-ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 68.59 grams (0.5 mol) of tyramine (β-hydroxyphenylethylamine), 109.13 grams (0.5 mol) of di-t-butylcarbonate, 27.83 grams (0.275 mol) of triethylamine and 2700 ml of 80:20 t-butanol:deionized water solution was stirred for 16 hours at room temperature. The volume of the reaction mixture was reduced to 500-600 ml using a rotary evaporator. The viscous solution was extracted three times with 500 ml portions of chloroform. The chloroform extractions were combined, dried with anhydrous sodium sulfate, filtered and the chloroform was removed under reduced pressure. The product crystallized slowly to form a waxy solid and was recrystallized from acetonitrile. Based on method of preparation, there was obtained 116.13 grams (98% yield) of N-t-butoxycarbonyl tyramine (N-BOC-tyramine). The identity of the chainstopper was further confirmed by 1H NMR analysis. a rotary evaporator The viscous solution was extracted three times with 500 ml portions of chloroform The chloroform extractions dried with anhydrous sodium sulfate filtered the chloroform was removed under reduced pressure The product crystallized slowly to form a waxy solid was recrystallized from acetonitrile Based on method of preparation

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-5-(trifluoromethyl) pyridine (3000 mg, 13.274 mmol), [2-(4-hydroxy-phenyl)ethyl]-carbamic acid tert-butyl ester (3150 mg, 13.274 mmol) and potassium carbonate anhydrous (2752 mg, 19.911 mmol) were dissolved in DMF (150 ml) and reaction was stirred at 60° C. overnight. The reaction mixture was washed with EtOAc and water (3×). Organic layers were combined and dried over phase separator filter tube affording the crude product which was purified on Biotage SP-1 system using 50 g Si SNAP column. The column containing sample was eluted with EtOAc/CyHex gradient (0-30% of EtOAc/30 CV). Fractions with desired product were gathered and solvent was evaporated to give the required product {2-[4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester as a white solid (2200 mg, yield=42.9%, purity 99%). [M+H]+=383.39 reaction The reaction mixture was washed with EtOAc and water (3×) dried over phase separator filter tube affording the crude product which was purified on Biotage SP-1 system The column containing sample was eluted with EtOAc/CyHex gradient (0-30% of EtOAc/30 CV) solvent was evaporated