methyl piperidine-1-carboxylate

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

Procedure: A mixture of (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid (61) (0.20 g, 0.49 mmol), HATU (0.37 g, 0.98 mmol), N-methylmorpholine (0.10 mL, 1.5 mmol) and methyl piperidinecarboxylate (0.2 mL, 2 mmol) in THF (10 mL) and DMF (2.0 mL) was stirred at room temperature for 18 h. The THF was evaporated under reduced pressure, the residue was quenched with water and the resulting solid was collected by filtration. The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 20:1) to give methyl 1-{[(1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-trien-5-yl]carbonyl}piperidine-4-carboxylate (97) (0.10 g, 37%) as a white solid. The THF was evaporated under reduced pressure the residue was quenched with water the resulting solid was collected by filtration The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 20:1)

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

Procedure: Polymer-bound piperidinecarboxylic acid, ethyl ester resin (0.25 g, 0.283 mmol) was swollen with a solution of MeOH (1 ml) in THF (4 ml) in a QUICKFIT test-tube. After addition of sodium methoxide (0.28 ml, 0.028 mmol, 1M solution in MeOH) the resulting suspension was stirred overnight at reflux. The reaction suspension was cooled down to room temperature and the resin was washed using VACMASTER station with DCM (4×3 ml), MeOH (2×3 ml) and then dried under vacuum. FT-IR (2% w/w KBr disk): C=0 1736 cm−1 (ester); 163 cm−1 (amide). at reflux the resin was washed dried under vacuum

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

Procedure: Polymer-bound piperidinecarboxylic acid, ethyl ester resin (0.25 g, 0.283 mmol) was swollen with a solution of MeOH (1 ml) in THF (4 ml) in a QUICKFIT test-tube. After addition of sodium methoxide (0.28 ml, 0.028 mmol, 1M solution in MeOH) the resulting suspension was stirred overnight at reflux. The reaction suspension was cooled down to room temperature and the resin was washed using VACMASTER station with DCM (4×3 ml), MeOH (2×3 ml) and then dried under vacuum. FT-IR (2% w/w KBr disk): C=0 1736 cm−1 (ester); 163 cm−1 (amide). at reflux the resin was washed dried under vacuum

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

Procedure: A mixture of (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid (61) (0.20 g, 0.49 mmol), HATU (0.37 g, 0.98 mmol), N-methylmorpholine (0.10 mL, 1.5 mmol) and methyl piperidinecarboxylate (0.2 mL, 2 mmol) in THF (10 mL) and DMF (2.0 mL) was stirred at room temperature for 18 h. The THF was evaporated under reduced pressure, the residue was quenched with water and the resulting solid was collected by filtration. The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 20:1) to give methyl 1-{[(1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-trien-5-yl]carbonyl}piperidine-4-carboxylate (97) (0.10 g, 37%) as a white solid. The THF was evaporated under reduced pressure the residue was quenched with water the resulting solid was collected by filtration The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 20:1)

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

Procedure: Polymer-bound piperidinecarboxylic acid, ethyl ester resin (0.25 g, 0.283 mmol) was swollen with a solution of MeOH (1 ml) in THF (4 ml) in a QUICKFIT test-tube. After addition of sodium methoxide (0.28 ml, 0.028 mmol, 1M solution in MeOH) the resulting suspension was stirred overnight at reflux. The reaction suspension was cooled down to room temperature and the resin was washed using VACMASTER station with DCM (4×3 ml), MeOH (2×3 ml) and then dried under vacuum. FT-IR (2% w/w KBr disk): C=0 1736 cm−1 (ester); 163 cm−1 (amide). at reflux the resin was washed dried under vacuum

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

Procedure: A mixture of (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid (61) (0.20 g, 0.49 mmol), HATU (0.37 g, 0.98 mmol), N-methylmorpholine (0.10 mL, 1.5 mmol) and methyl piperidinecarboxylate (0.2 mL, 2 mmol) in THF (10 mL) and DMF (2.0 mL) was stirred at room temperature for 18 h. The THF was evaporated under reduced pressure, the residue was quenched with water and the resulting solid was collected by filtration. The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 20:1) to give methyl 1-{[(1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-trien-5-yl]carbonyl}piperidine-4-carboxylate (97) (0.10 g, 37%) as a white solid. The THF was evaporated under reduced pressure the residue was quenched with water the resulting solid was collected by filtration The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 20:1)