N-CBZ-CIS-4-HYDROXY-D-PROLINE METHYL ESTER

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

Procedure: A solution of 20 g (71.6 mmol) of N-Cbz-cis-4-hydroxy-D-proline methyl ester, 15 mL (107 mmol) of triethylamine and 0.4 g (3.3 mmol) of 4-dimethylaminopyridine in 200 mL of CHCl3 was treated with 15.1 g (79.2 mmol) of p-toluenesulfonyl chloride in portions. The reaction was stirred at room temperature for 18 hours and was washed successively with 100 mL of H2O, 100 mL of 1N aqueous citric acid, and 100 mL of H2O. The organic fraction was dried over Na2SO4 and evaporated in vacuo to give 31.4 g of an oil which was purified by flash chromatography (SiO2 ; 50 percent EtOAc in hexanes) to afford 18.2 g (42 mmol; 59 percent) of the title compound as a white solid. was washed successively with 100 mL of H2O, 100 mL of 1N aqueous citric acid, and 100 mL of H2O The organic fraction was dried over Na2SO4 evaporated in vacuo

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

Procedure: The title compound was prepared from 3-hydroxy pyridine and N-Cbz-cis-4-hydroxy-D-proline methyl ester by substantially following the procedure used in the preparation of N-Cbz-trans-4-(2-naphthyloxy)-D-proline methyl ester, Example 6, Steps A and B.

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

Procedure: A solution of 15.0 g (53.7 mmol) of N-Cbz-cis-4-hydroxy-D-proline methyl ester, 11.3 g (78.4 mmol) of β-naphthol, and 20.5 g (78.2 mmol) of triphenylphosphine in 300 mL of THF was treated with 12.3 mL (78.1 mmol) of diethyl azidodicarboxylate over 0.5 hour. The reaction was stirred at room temperature for 18 hours and was quenched by the addition of 100 mL sat'd aq NaCl. The two layers were separated and the organic solution dried (Na2SO4). Evaporation of the solvent gave 46.2 g of an oil which was purified by flash chromatography (SiO2 ; gradient of 25 percent to 50 percent EtOAc in hexanes) to afford 15.2 g (37.5 mmol; 70 percent) of the title compound. was quenched by the addition of 100 mL The two layers were separated the organic solution dried (Na2SO4) Evaporation of the solvent

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

Procedure: A solution of 20 g (71.6 mmol) of N-Cbz-cis-4-hydroxy-D-proline methyl ester, 15 mL (107 mmol) of triethylamine and 0.4 g (3.3 mmol) of 4-dimethylaminopyridine in 200 mL of CHCl3 was treated with 15.1 g (79.2 mmol) of p-toluenesulfonyl chloride in portions. The reaction was stirred at room temperature for 18 hours and was washed successively with 100 mL of H2O, 100 mL of 1N aqueous citric acid, and 100 mL of H2O. The organic fraction was dried over Na2SO4 and evaporated in vacuo to give 31.4 g of an oil which was purified by flash chromatography (SiO2 ; 50 percent EtOAc in hexanes) to afford 18.2 g (42 mmol; 59 percent) of the title compound as a white solid. was washed successively with 100 mL of H2O, 100 mL of 1N aqueous citric acid, and 100 mL of H2O The organic fraction was dried over Na2SO4 evaporated in vacuo

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

Procedure: The title compound was prepared from 3-hydroxy pyridine and N-Cbz-cis-4-hydroxy-D-proline methyl ester by substantially following the procedure used in the preparation of N-Cbz-trans-4-(2-naphthyloxy)-D-proline methyl ester, Example 6, Steps A and B.

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

Procedure: A solution of 15.0 g (53.7 mmol) of N-Cbz-cis-4-hydroxy-D-proline methyl ester, 11.3 g (78.4 mmol) of β-naphthol, and 20.5 g (78.2 mmol) of triphenylphosphine in 300 mL of THF was treated with 12.3 mL (78.1 mmol) of diethyl azidodicarboxylate over 0.5 hour. The reaction was stirred at room temperature for 18 hours and was quenched by the addition of 100 mL sat'd aq NaCl. The two layers were separated and the organic solution dried (Na2SO4). Evaporation of the solvent gave 46.2 g of an oil which was purified by flash chromatography (SiO2 ; gradient of 25 percent to 50 percent EtOAc in hexanes) to afford 15.2 g (37.5 mmol; 70 percent) of the title compound. was quenched by the addition of 100 mL The two layers were separated the organic solution dried (Na2SO4) Evaporation of the solvent