(E)-3-phenylprop-2-en-1-ol

Conditions: temp:17.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium carbonate (224 g) and trans-cinnamyl alcohol (200.0 g) were mixed with 2 L of methylene chloride, a slow nitrogen sweep was maintained through the vapor space of the flask and the mixture was cooled to 15-20° C. with a cold water bath. Peracetic acid solution (35%, 381.2 mL) was added over a 3 hour period, maintaining the internal temperature below 25° C. After the peracetic acid addition was complete, the mixture was stirred for 2-3 hours until complete, as shown by HPLC analysis. The mixture was cooled to 10° C. with an ice bath, and a solution of sodium sulfite (160 g) in 1200 ml water was added slowly over 90 minutes, keeping the temperature below 30° C. The phases were separated and the aqueous phase was extracted with methylene chloride (200 mL) to give a solution of the title compound. a slow nitrogen sweep was maintained through the vapor space of the flask maintaining the internal temperature below 25° C The mixture was cooled to 10° C. with an ice bath the temperature below 30° C The phases were separated the aqueous phase was extracted with methylene chloride (200 mL)

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

Procedure: Step 1 A suspension of (E)-3-phenylprop-2-en-1-ol (2.22 g, 16.51 mmol) and 2-methylbenzene-1,3-diol (2.05 g, 16.51 mmol) in 1,2-dichloroethane (100 mL) was treated with p-toluenesulfonic acid monohydrate (0.157 g, 0.826 mmol) and the mixture was heated at reflux for 1 h. The mixture was cooled to rt and concentrated, and the residue was subjected to column chromatography (eluting with a gradient from 90:10 to 75:25 hexane-EtOAc) provided a mixture of 4-cinnamyl-2-methylbenzene-1,3-diol and 4,6-dicinnamyl-2-methylbenzene-1,3-diol (2:1, 1.97 g). This material (1.89 g) was dissolved in toluene (60 mL) and treated with p-toluenesulfonic acid monohydrate (299 mg, 1.57 mmol) and heated at reflux for 6 h. The mixture was cooled to rt, diluted with EtOAc (100 mL), washed with NaHCO3 (aq) (2×30 mL), water (30 mL) and brine (30 mL), dried and concentrated. Column chromatography (eluting with a gradient from 95:5 to 70:30 hexane-EtOAc) provided 8-methyl-2-phenylchroman-7-ol as a brown liquid (ca. 85% purity, 672 mg, 17%) used without further purification. 1H NMR (400 MHz, chloroform-d) δ 7.35-7.50 (4 H, m), 7.27-7.35 (1H, m), 6.79 (1H, d, J=8.36 Hz), 6.38 (1H, d, J=8.14 Hz), 5.07 (1H, dd, J=10.12, 2.42 Hz), 4.64 (1H, s), 2.83-3.02 (1H, m), 2.71 (1H, ddd, J=16.01, 4.90, 3.74 Hz), 2.16-2.27 (1H, m), 2.14 (3H, s), 1.86-2.04 (1H, m). Mass spectrum m/z 241.0 (M+H)+. the mixture was heated at reflux for 1 h concentrated eluting with a gradient from 90:10 to 75:25 hexane-EtOAc) provided heated at reflux for 6 h The mixture was cooled to rt washed with NaHCO3 (aq) (2×30 mL), water (30 mL) and brine (30 mL) dried concentrated Column chromatography (eluting with a gradient from 95:5 to 70:30 hexane-EtOAc)

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

Procedure: Step 1 A suspension of (E)-3-phenylprop-2-en-1-ol (2.22 g, 16.51 mmol) and 2-methylbenzene-1,3-diol (2.05 g, 16.51 mmol) in 1,2-dichloroethane (100 mL) was treated with p-toluenesulfonic acid monohydrate (0.157 g, 0.826 mmol) and the mixture was heated at reflux for 1 h. The mixture was cooled to rt and concentrated, and the residue was subjected to column chromatography (eluting with a gradient from 90:10 to 75:25 hexane-EtOAc) provided a mixture of 4-cinnamyl-2-methylbenzene-1,3-diol and 4,6-dicinnamyl-2-methylbenzene-1,3-diol (2:1, 1.97 g). This material (1.89 g) was dissolved in toluene (60 mL) and treated with p-toluenesulfonic acid monohydrate (299 mg, 1.57 mmol) and heated at reflux for 6 h. The mixture was cooled to rt, diluted with EtOAc (100 mL), washed with NaHCO3 (aq) (2×30 mL), water (30 mL) and brine (30 mL), dried and concentrated. Column chromatography (eluting with a gradient from 95:5 to 70:30 hexane-EtOAc) provided 8-methyl-2-phenylchroman-7-ol as a brown liquid (ca. 85% purity, 672 mg, 17%) used without further purification. 1H NMR (400 MHz, chloroform-d) δ 7.35-7.50 (4 H, m), 7.27-7.35 (1H, m), 6.79 (1H, d, J=8.36 Hz), 6.38 (1H, d, J=8.14 Hz), 5.07 (1H, dd, J=10.12, 2.42 Hz), 4.64 (1H, s), 2.83-3.02 (1H, m), 2.71 (1H, ddd, J=16.01, 4.90, 3.74 Hz), 2.16-2.27 (1H, m), 2.14 (3H, s), 1.86-2.04 (1H, m). Mass spectrum m/z 241.0 (M+H)+. the mixture was heated at reflux for 1 h concentrated eluting with a gradient from 90:10 to 75:25 hexane-EtOAc) provided heated at reflux for 6 h The mixture was cooled to rt washed with NaHCO3 (aq) (2×30 mL), water (30 mL) and brine (30 mL) dried concentrated Column chromatography (eluting with a gradient from 95:5 to 70:30 hexane-EtOAc)

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

Procedure: 50 g (0,36 mol) of cinnamic alcohol are dissolved in 180 ml of dry toluene. 20 g (0,36 mol) of KOH are added to the solution, and the resulting mixture is kept under stirring for one hour at room temperature. During this phase, potassium cinnamate is obtained. Then, a solution prepared starting from 18 g (0,10 mol) of 2,4,6-trichloro-s-triazine in 150 ml of toluene is added, allowing to react at room temperature for further 90 hours under stirring.

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

Procedure: 50 g (0,36 mol) of cinnamic alcohol are dissolved in 180 ml of dry toluene. 20 g (0,36 mol) of KOH are added to the solution, and the resulting mixture is kept under stirring for one hour at room temperature. During this phase, potassium cinnamate is obtained. Then, a solution prepared starting from 18 g (0,10 mol) of 2,4,6-trichloro-s-triazine in 150 ml of toluene is added, allowing to react at room temperature for further 90 hours under stirring.

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

Procedure: Indole--10% in Diethyl Phthalate: 2%

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

Procedure: Indole--10% in Diethyl Phthalate: 2%

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

Procedure: A mixture of 187 parts of cinnamic alcohol, 360 parts of 3,3-dimethylacrolein and 550 parts of toluene is heated with 33 parts of glacial acetic acid in a V4A steel stirred vessel having a capacity of 5 liters for six hours at 140° C. at a pressure of 2 atmospheres, the water forming being continuously removed as an azeotropic mixture with toluene. The product is distilled. 149 parts of 3-methyl-7-phenyl-2,6-heptadien-1-al is obtained having a boiling point of 118° to 120° C. at 10-3 mm. The yield is 81% of theory (based on cinnamic alcohol) at a conversion of 66%. for six hours at 140° C. the water forming being continuously removed as an azeotropic mixture with toluene The product is distilled

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

Procedure: Using the procedure described previously, a solution of L-isoleucine, N-[1-(carboxymethyl)-L-prolyl] benzylamide (65 mg, 0.17 mmol), 4-N,N-dimethylaminopyridine (12.5 mg, 0.10 mmol, 0.6 eq), 1,3-dicyclohexylcarbodiimide (64 mg, 0.31 mmol, 1.8 eq) in dichloromethane (5.0 mL) was treated with trans cinnamyl alcohol (29 uL, 0.22 mmol, 1.3 eq). After TLC indicated the reaction was complete, the mixture was purified by HPLC to provide 32 mg (38%) of L-isoleucine, N-[1-(2-(3-phenyl-2-propen-1-oxy)-2 -oxoethyl)-L-prolyl] benzylamide. the mixture was purified by HPLC

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

Procedure: Using the procedure described previously, a solution of L-isoleucine, N-[1-(carboxymethyl)-L-prolyl] benzylamide (65 mg, 0.17 mmol), 4-N,N-dimethylaminopyridine (12.5 mg, 0.10 mmol, 0.6 eq), 1,3-dicyclohexylcarbodiimide (64 mg, 0.31 mmol, 1.8 eq) in dichloromethane (5.0 mL) was treated with trans cinnamyl alcohol (29 uL, 0.22 mmol, 1.3 eq). After TLC indicated the reaction was complete, the mixture was purified by HPLC to provide 32 mg (38%) of L-isoleucine, N-[1-(2-(3-phenyl-2-propen-1-oxy)-2 -oxoethyl)-L-prolyl] benzylamide. the mixture was purified by HPLC

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

Procedure: Step 1 A suspension of (E)-3-phenylprop-2-en-1-ol (2.22 g, 16.51 mmol) and 2-methylbenzene-1,3-diol (2.05 g, 16.51 mmol) in 1,2-dichloroethane (100 mL) was treated with p-toluenesulfonic acid monohydrate (0.157 g, 0.826 mmol) and the mixture was heated at reflux for 1 h. The mixture was cooled to rt and concentrated, and the residue was subjected to column chromatography (eluting with a gradient from 90:10 to 75:25 hexane-EtOAc) provided a mixture of 4-cinnamyl-2-methylbenzene-1,3-diol and 4,6-dicinnamyl-2-methylbenzene-1,3-diol (2:1, 1.97 g). This material (1.89 g) was dissolved in toluene (60 mL) and treated with p-toluenesulfonic acid monohydrate (299 mg, 1.57 mmol) and heated at reflux for 6 h. The mixture was cooled to rt, diluted with EtOAc (100 mL), washed with NaHCO3 (aq) (2×30 mL), water (30 mL) and brine (30 mL), dried and concentrated. Column chromatography (eluting with a gradient from 95:5 to 70:30 hexane-EtOAc) provided 8-methyl-2-phenylchroman-7-ol as a brown liquid (ca. 85% purity, 672 mg, 17%) used without further purification. 1H NMR (400 MHz, chloroform-d) δ 7.35-7.50 (4 H, m), 7.27-7.35 (1 H, m), 6.79 (1 H, d, J=8.36 Hz), 6.38 (1 H, d, J=8.14 Hz), 5.07 (1 H, dd, J=10.12, 2.42 Hz), 4.64 (1 H, s), 2.83-3.02 (1 H, m), 2.71 (1 H, ddd, J=16.01, 4.90, 3.74 Hz), 2.16-2.27 (1 H, m), 2.14 (3 H, s), 1.86-2.04 (1 H, m). Mass spectrum m/z 241.0 (M+H)+. the mixture was heated at reflux for 1 h concentrated eluting with a gradient from 90:10 to 75:25 hexane-EtOAc) provided heated at reflux for 6 h The mixture was cooled to rt washed with NaHCO3 (aq) (2×30 mL), water (30 mL) and brine (30 mL) dried concentrated Column chromatography (eluting with a gradient from 95:5 to 70:30 hexane-EtOAc)

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

Procedure: A mixture of 187 parts of cinnamic alcohol, 360 parts of 3,3-dimethylacrolein and 550 parts of toluene is heated with 33 parts of glacial acetic acid in a V4A steel stirred vesel having a capacity of 5 liters for six hours at 140°C at a pressure of 2 atmospheres, the water forming being continuously removed as an azeotropic mixture with toluene. The product is distilled. 149 parts of 3-methyl-7-phenyl-2,6-heptadien-1-al is obtained having a boiling point of 118° to 120°C at 10-3 mm. The yield is 81% of theory (based on cinnamic alcohol) at a conversion of 66%. for six hours at 140°C the water forming being continuously removed as an azeotropic mixture with toluene The product is distilled