2-chloroethyl formate

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

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

Procedure: Under atmosphere of argon, to a solution of (2S)-2-(t-butoxycarbonylamino)-4-methylpentanoic acid (t-butoxycarbonyl-L-leucine) (37.4 g) in tetrahydrofuran (800 ml) was added N-methylmorpholine (33 ml) at −25° C. and the mixture was stirred for 10 minutes. To the mixture was added chloroethylformate (15.8 ml) and the mixture was stirred for 20 minutes. Thereto was added a solution of diazomethane in diethyl ether and the mixture was stirred for another 2 hours. Thereto was added a mixture of 47% hydrobromic acid-acetic acid (1:1) at 0° C. and the mixture was stirred for 15 minutes. To the reaction mixture was added water and was extracted with a mixture of ethyl acetate-hexane. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and was concentrated. The residue was washed with cooled hexane to give the title compound (27.4 g) having the following physical data. the mixture was stirred for 20 minutes the mixture was stirred for another 2 hours Thereto was added the mixture was stirred for 15 minutes was extracted with a mixture of ethyl acetate-hexane The organic layer was washed with a saturated aqueous solution of sodium bicarbonate a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate was concentrated The residue was washed with cooled hexane

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

Procedure: A suspension of 17.3 g (0.36 mol) of 50% NaH in mineral oil in 100 mL of diglyme was treated with a solution of 33.9 g (0.36 mol) of phenol in 50 mL of diglyme. The resulting mixture was stirred overnight and then charged into a 400 mL metal tube along with 38.6 g (0.36 mol) of 2-chloroethyl formate and 40 g (0.40 mol) of tetrafluoroethylene. The resulting mixture was agitated for 12 h, and then added to 1 L of cold water, thereby causing the formation of layers. The lower layer was washed with water, dried over CaSO4, and distilled to afford 54.5 g (57% yield) of 2-(2-phenoxytetrafluoro-ethyl)-1,3-dioxolane, b.p. 62°-65° at 8 Pa (0.06 mm). The IR (neat) and NMR (CCl4) spectra of the product were consistent with the assigned structure. Anal.: Calcd. for C11H10F4O3 :C, 49.63; H, 3.79l F, 28.55. Found: C, 49 90; H, 3.80; F, 28.91. The resulting mixture was agitated for 12 h The lower layer was washed with water dried over CaSO4 distilled

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound from Step B (60 mg) was dissolved in DCE (10 mL) and chloroethylformate (0.2 mmol) was added. The mixture was heated at 80-100° C. for 1 h and concentrated. The residue was dissolved in MeOH (3 mL) and heated at 150° C. in a microwave reactor for another 1 h. The mixture was cooled to rt and purified via PTLC providing the title compound (30 mg). MS (ESI): mass calcd. for C17H17BrClNO2, 381.0; m/z found, 382.0 [M+H]+. 1H NMR (CDCl3): 7.43-7.23 (m, 4H), 7.12-7.06 (m, 1H), 6.86-6.78 (m, 2H), 5.12 (s, 2H), 4.24-4.16 (m, 2H), 3.78-3.67 (m, 2H), 1.67 (s, 3H). concentrated The residue was dissolved in MeOH (3 mL) heated at 150° C. in a microwave reactor for another 1 h The mixture was cooled to rt purified via PTLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 106.3 g (0.88 mol) of chloroethylformate are added dropwise with stirring over a period of 30 minutes to a solution of 100 g (0.48 mol) of 1-methyl-4-ethoxycarbonyl-mercapto-piperidine in 80 ml of toluene which has been heated to 90° C. The solution is then heated for two hours to from 100° to 110° C. After repeated addition of 40 g of chloroethylformate the solution is heated for a further three hours. After leaving it to stand overnight at room temperature it is drawn off by suction using a glass fibre filter. The solution is concentrated on a rotary evaporator and the residue is distilled off. 20 g (94% of the theoretical yield) of 1-ethoxycarbonyl-4-ethoxycarbonyl-mercapto-piperidine are obtained. B.P. 138°-140° C. The solution is then heated for two hours to from 100° to 110° C is heated for a further three hours After leaving it The solution is concentrated on a rotary evaporator the residue is distilled off

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

Procedure: A suspension of 17.3 g (0.36 mol) of 50% NaH in mineral oil in 100 mL of diglyme was treated with a solution of 33.9 g (0.36 mol) of phenol in 50 mL of diglyme. The resulting mixture was stirred overnight and then charged into a 400 mL metal tube along with 38.6 g (0.36 mol) of 2-chloroethyl formate and 40 g (0.40 mol) of tetrafluoroethylene. The resulting mixture was agitated for 12 h, and then added to 1 L of cold water, thereby causing the formation of layers. The lower layer was washed with water, dried over CaSO4, and distilled to afford 54.5 g (57% yield) of 2-(2-phenoxytetrafluoro-ethyl)-1,3-dioxolane, b.p. 62°-65° at 8 Pa (0.06 mm). The IR (neat) and NMR (CCl4) spectra of the product were consistent with the assigned structure. Anal.: Calcd. for C11H10F4O3 : C, 49.63; H, 3.79; F, 28.55. Found: C, 49 90; H, 3.80; F, 28.91. The resulting mixture was agitated for 12 h The lower layer was washed with water dried over CaSO4 distilled

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 6-(2-methoxy-phenyl)-pyrimidin-4-ylamine (XXIV) (1.0 g, 4.9 mmol) and potassium carbonate (4.0 g, 29 mmol) in 2-butanone (10 ml), chloroethylformate (0.50 ml, 4.9 mmol) was added and the mixture was refluxed for 3 hours at 80° C. The reaction was monitored by TLC. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to provide 0.60 g of [6-(2-methoxy-phenyl)-pyrimidin-4-yl]-carbamic acid ethyl ester (XL). was added was added the mixture was extracted with ethyl acetate The organic layer was separated dried over anhydrous sodium sulfate concentrated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 6-(2-methoxy-phenyl)-pyrimidin-4-ylamine (XXIV) (1.0 g, 4.9 mmol) and potassium carbonate (4.0 g, 29 mmol) in 2-butanone (10 ml), chloroethylformate (0.50 ml, 4.9 mmol) was added and the mixture was refluxed for 3 hours at 80° C. The reaction was monitored by TLC. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to provide 0.60 g of [6-(2-methoxy-phenyl)-pyrimidin-4-yl]-carbamic acid ethyl ester (XL). was added was added the mixture was extracted with ethyl acetate The organic layer was separated dried over anhydrous sodium sulfate concentrated

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

Procedure: A suspension of 17.3 g (0.36 mol) of 50% NaH in mineral oil in 100 mL of diglyme was treated with a solution of 33.9 g (0.36 mol) of phenol in 50 mL of diglyme. The resulting mixture was stirred overnight and then charged into a 400 mL metal tube along with 38.6 g (0.36 mol) of 2-chloroethyl formate and 40 g (0.40 mol) of tetrafluoroethylene. The resulting mixture was agitated for 12 h, and then added to 1 L of cold water, thereby causing the formation of layers. The lower layer was washed with water, dried over CaSO4, and distilled to afford 54.5 g (57% yield) of 2-(2-phenoxytetrafluoro-ethyl)-1,3-dioxolane, b.p. 62°-65° at 8 Pa (0.06 mm). The IR (neat) and NMR (CCl4) spectra of the product were consistent with the assigned structure. Anal.: Calcd. for C11H10F4O3 : C, 49.63; H, 3.79; F, 28.55. Found: C, 49.90; H, 3.80; F, 28.91. The resulting mixture was agitated for 12 h The lower layer was washed with water dried over CaSO4 distilled

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

Procedure: Under atmosphere of argon, to a solution of (2S)-2-(t-butoxycarbonylamino)-4-methylpentanoic acid (t-butoxycarbonyl-L-leucine) (37.4 g) in tetrahydrofuran (800 ml) was added N-methylmorpholine (33 ml) at −25° C. and the mixture was stirred for 10 minutes. To the mixture was added chloroethylformate (15.8 ml) and the mixture was stirred for 20 minutes. Thereto was added a solution of diazomethane in diethyl ether and the mixture was stirred for another 2 hours. Thereto was added a mixture of 47% hydrobromic acid-acetic acid (1:1) at 0° C. and the mixture was stirred for 15 minutes. To the reaction mixture was added water and was extracted with a mixture of ethyl acetate-hexane. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and was concentrated. The residue was washed with cooled hexane to give the title compound (27.4 g) having the following physical data. the mixture was stirred for 20 minutes the mixture was stirred for another 2 hours Thereto was added the mixture was stirred for 15 minutes was extracted with a mixture of ethyl acetate-hexane The organic layer was washed with a saturated aqueous solution of sodium bicarbonate a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate was concentrated The residue was washed with cooled hexane

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

Procedure: A suspension of 17.3 g (0.36 mol) of 50% NaH in mineral oil in 100 mL of diglyme was treated with a solution of 33.9 g (0.36 mol) of phenol in 50 mL of diglyme. The resulting mixture was stirred overnight and then charged into a 400 mL metal tube along with 38.6 g (0.36 mol) of 2-chloroethyl formate and 40 g (0.40 mol) of tetrafluoroethylene. The resulting mixture was agitated for 12 h, and then added to 1 L of cold water, thereby causing the formation of layers. The lower layer was washed with water, dried over CaSO4, and distilled to afford 54.5 g (57% yield) of 2-(2-phenoxytetrafluoro-ethyl)-1,3-dioxolane, b.p. 62°-65° at 8 Pa (0.06 mm). The IR (neat) and NMR (CCl4) spectra of the product were consistent with the assigned structure. Anal.: Calcd. for C11H10F4O3 :C, 49.63; H, 3.79l F, 28.55. Found: C, 49 90; H, 3.80; F, 28.91. The resulting mixture was agitated for 12 h The lower layer was washed with water dried over CaSO4 distilled

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

Procedure: A suspension of 17.3 g (0.36 mol) of 50% NaH in mineral oil in 100 mL of diglyme was treated with a solution of 33.9 g (0.36 mol) of phenol in 50 mL of diglyme. The resulting mixture was stirred overnight and then charged into a 400 mL metal tube along with 38.6 g (0.36 mol) of 2-chloroethyl formate and 40 g (0.40 mol) of tetrafluoroethylene. The resulting mixture was agitated for 12 h, and then added to 1 L of cold water, thereby causing the formation of layers. The lower layer was washed with water, dried over CaSO4, and distilled to afford 54.5 g (57% yield) of 2-(2-phenoxytetrafluoro-ethyl)-1,3-dioxolane, b.p. 62°-65° at 8 Pa (0.06 mm). The IR (neat) and NMR (CCl4) spectra of the product were consistent with the assigned structure. Anal.: Calcd. for C11H10F4O3 :C, 49.63; H, 3.79l F, 28.55. Found: C, 49 90; H, 3.80; F, 28.91. The resulting mixture was agitated for 12 h The lower layer was washed with water dried over CaSO4 distilled