methyl 4-aminothiane-4-carboxylate

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: To a solution of HCl salt of 4-amino-tetrahydro-thiopyran-4-carboxylic acid methyl ester (529 mg, 2.5 mmol), 2-hydroxy-3-methyl-benzoic acid (380 mg, 2.5 mmol), HATU (1.14 g, 3.0 mmol) in anhydrous DMF (20 mL) is added DIPEA (1.66 mL, 10 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (30 mL) and washed with water (1×10 mL) and brine (2×10 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 10-80% EtOAc in heptane) to give a pure product (27) as white solid (102 mg, 13%). After the removal of DMF in vacuo the residue is dissolved in EtOAc (30 mL) washed with water (1×10 mL) and brine (2×10 mL) The organic layer is dried over anhydrous Na2SO4 concentrated in vacuo The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 10-80% EtOAc in heptane)

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

Procedure: To a solution of HCl salt of 4-amino-tetrahydro-thiopyran-4-carboxylic acid methyl ester (529 mg, 2.5 mmol), 2-hydroxy-3-methyl-benzoic acid (380 mg, 2.5 mmol), HATU (1.14 g, 3.0 mmol) in anhydrous DMF (20 mL) is added DIPEA (1.66 mL, 10 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (30 mL) and washed with water (1×10 mL) and brine (2×10 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 10-80% EtOAc in heptane) to give a pure product (27) as white solid (102 mg, 13%). After the removal of DMF in vacuo the residue is dissolved in EtOAc (30 mL) washed with water (1×10 mL) and brine (2×10 mL) The organic layer is dried over anhydrous Na2SO4 concentrated in vacuo The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 10-80% EtOAc in heptane)

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

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

Procedure: To a solution of HCl salt of 4-amino-tetrahydro-thiopyran-4-carboxylic acid methyl ester (529 mg, 2.5 mmol), 2-hydroxy-3-methyl-benzoic acid (380 mg, 2.5 mmol), HATU (1.14 g, 3.0 mmol) in anhydrous DMF (20 mL) is added DIPEA (1.66 mL, 10 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (30 mL) and washed with water (1×10 mL) and brine (2×10 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 10-80% EtOAc in heptane) to give a pure product (27) as white solid (102 mg, 13%). After the removal of DMF in vacuo the residue is dissolved in EtOAc (30 mL) washed with water (1×10 mL) and brine (2×10 mL) The organic layer is dried over anhydrous Na2SO4 concentrated in vacuo The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 10-80% EtOAc in heptane)