prop-2-ynyl carbonochloridate

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: Analogous to Example 19, 2,7-dihydroxynaphthalene was reacted with propargyl chloroformate to produce the title compound. Yield was 83.6% theory. m.p. 94°-96° C. IR (cm-1) 3330, 2100, 1755, 1610, 1510 1H-NMR (δ, ppm) 2.42 (CH≡C--), 4.86 (≡C--CH2 --), 7.20, 8.10 (Ph)

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

Procedure: Analogous to Example 19, 2,7-dihydroxynaphthalene was reacted with propargyl chloroformate to produce the title compound. Yield was 83.6% theory. m.p. 94°-96° C. IR (cm-1) 3330, 2100, 1755, 1610, 1510 1H-NMR (δ, ppm) 2.42 (CH≡C--), 4.86 (≡C--CH2 --), 7.20, 8.10 (Ph)

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

Procedure: A flask equipped with a stirrer, thermometer, nitrogen gas tube and reflux condenser was charged with 18.6 g of 4,4'-dihydroxybiphenyl and 23.0 g of trimethylamine in 50.0 g of methylene chloride. To the flask was added 26.0 g of propargyl chloroformate dropwise over one hour and the mixture was allowed to react for 6 hours at 30° C. After the reaction, the reaction mixture was treated with methylene chloride-water mixture and the organic phase was separated followed by drying over magnesium sulfate overnight. After filtering, the filtrate was evaporated in a rotary evaporator. The resulting crystals were recrystallized to give the title compound at a yield of 93.6% of theory. A flask equipped with a stirrer thermometer, nitrogen gas tube and reflux condenser to react for 6 hours at 30° C After the reaction the organic phase was separated by drying over magnesium sulfate overnight After filtering the filtrate was evaporated in a rotary evaporator The resulting crystals were recrystallized

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

Procedure: A flask equipped with a stirrer, thermometer, nitrogen gas tube and reflux condenser was charged with 18.6 g of 4,4'-dihydroxybiphenyl and 23.0 g of trimethylamine in 50.0 g of methylene chloride. To the flask was added 26.0 g of propargyl chloroformate dropwise over one hour and the mixture was allowed to react for 6 hours at 30° C. After the reaction, the reaction mixture was treated with methylene chloride-water mixture and the organic phase was separated followed by drying over magnesium sulfate overnight. After filtering, the filtrate was evaporated in a rotary evaporator. The resulting crystals were recrystallized to give the title compound at a yield of 93.6% of theory. A flask equipped with a stirrer thermometer, nitrogen gas tube and reflux condenser to react for 6 hours at 30° C After the reaction the organic phase was separated by drying over magnesium sulfate overnight After filtering the filtrate was evaporated in a rotary evaporator The resulting crystals were recrystallized

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

Procedure: A flask equipped with a stirrer, thermometer, nitrogen gas tube and reflux condenser was charged with 20.0 g of bis(4-hydroxyphenyl)methane, 50.0 g of methylene chloride and 23.0 g of trimethylamine. To the flask was added 26.0 g of propargyl chloroformate dropwise over one hour and the mixture was allowed to react for 6 hours at 30° C. After the reaction, the reaction mixture was treated with methylene chloride-water mixture and the organic phase was separated followed by drying over magnesium sulfate overnight. After filtering, the filtrate was evaporated in a rotary evaporator. The resulting crystals were recrystallized to give the title compound melting at 60° C. at a yield of 93.6% of theory. A flask equipped with a stirrer thermometer, nitrogen gas tube and reflux condenser to react for 6 hours at 30° C After the reaction the organic phase was separated by drying over magnesium sulfate overnight After filtering the filtrate was evaporated in a rotary evaporator The resulting crystals were recrystallized

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

Procedure: A flask equipped with a stirrer, thermometer, nitrogen gas tube and reflux condenser was charged with 20.0 g of bis(4-hydroxyphenyl)methane, 50.0 g of methylene chloride and 23.0 g of trimethylamine. To the flask was added 26.0 g of propargyl chloroformate dropwise over one hour and the mixture was allowed to react for 6 hours at 30° C. After the reaction, the reaction mixture was treated with methylene chloride-water mixture and the organic phase was separated followed by drying over magnesium sulfate overnight. After filtering, the filtrate was evaporated in a rotary evaporator. The resulting crystals were recrystallized to give the title compound melting at 60° C. at a yield of 93.6% of theory. A flask equipped with a stirrer thermometer, nitrogen gas tube and reflux condenser to react for 6 hours at 30° C After the reaction the organic phase was separated by drying over magnesium sulfate overnight After filtering the filtrate was evaporated in a rotary evaporator The resulting crystals were recrystallized

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

Procedure: 1-(azepan-4-yl)-N-(2-methylpropyl)piperidine-4-carboxamide TFA salt (0.15 g, 0.38 mmol) was dissolved in DCM (8 mL) at rt. NEt3 (0.16 mL, 1.14 mmol) and propargyl chloroformate (0.06 mL, 0.57 mmol) were added and the reaction mixture was stirred at rt for 2 h under nitrogen. The solvents were removed in vacuo, and the residue was partitioned between DCM and sat. NaHCO3 sol.), organic layer washed with sat. NaCl sol. and dried over MgSO4. The residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 10 g, 40-63 μm, 60 Å, 12 mL per min, gradient 0% to 10% MeOH in DCM]) to give prop-2-yn-1-yl-4-(4-((2-methylpropyl)carbamoyl)piperidin-1-yl)azepane-1-carboxylate (0.04 g, 31%) as a yellow gum. The solvents were removed in vacuo the residue was partitioned between DCM and sat. NaHCO3 sol.), organic layer washed with sat. NaCl sol. dried over MgSO4 The residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 10 g, 40-63 μm, 60 Å, 12 mL per min, gradient 0% to 10% MeOH in DCM])

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

Procedure: In analogy to the procedure described for the synthesis of example 2 (step b), the title compound rac-{(3R,4S)-4-(3,4-dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid prop-2-ynyl ester was prepared from rac-{4-[(3S,4R)-3-(3,4-dichloro-phenyl)-4-methylamino-pyrrolidine-1-carbonyl]-piperidin-1-yl}-(1-methyl-cyclopropyl)-methanone using propargyl chloroformate instead of 4-fluorophenyl chloroformate and was obtained as a yellow foam. MS m/e: 552.3 [M]+. In analogy to the procedure described for the synthesis of example 2 (step b) was obtained as a yellow foam