tert-butyl 6-methyl-2,2-dioxooxathiazinane-3-carboxylate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of 60% NaH dispersion in mineral oil (78.8 mg, 2.0 mmol) in DMF (2.5 mL) cooled to 0° C. is added a solution of diethyl 1H-indole-2,6-dicarboxylate (Intermediate A, 561 mg, 2.1 mmol) in DMF (3 mL). The mixture is stirred for 20 min and a solution of tert-butyl 6-methyl-1,2,3-oxathiazinane-3-carboxylate 2,2-dioxide (450 mg, 1.8 mmol) in DMF (2.5 mL) is added. The reaction mixture is stirred for 30 min at 0° C. and it is warmed to room temperature and stirred for 48 h. Saturated NH4Cl solution is added and the reaction mixture is extracted with EtOAc. The organic layer is separated, washed with water, then brine, dried (MgSO4) and concentrated to afford the title compound (1.04 g, 50% pure) as an oil. The reaction mixture is stirred for 30 min at 0° C. it is warmed to room temperature stirred for 48 h the reaction mixture is extracted with EtOAc The organic layer is separated washed with water brine, dried (MgSO4) concentrated

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

Procedure: To a solution of tert-butyl 6-methyl-1,2,3-oxathiazinane-3-carboxylate 2-oxide (2.52 g, 10.7 mmol) in acetonitrile (25 mL) and water (15 mL) cooled to 0° C. is added sodium periodate (3.4 g, 16.1 mmol) in one portion. After 5 min, the pH is adjusted to 7-8 by addition of saturated Na2HPO4 solution. A solution of RuCl3 (22 mg, 0.11 mmol) in water (0.5 mL) is added and the pH is kept between 6 and 9 by addition of Na2HPO4 solution. After 2 h, water (100 mL) is added and pH is adjusted to 6 by addition of 2M HCl solution. The reaction mixture is extracted with EtOAc and the organic layer is washed with NaHCO3 and brine and the washes are back-extracted once with EtOAc. Then the combined organic layers are dried (MgSO4), filtered and concentrated. The crude compound is purified by flash column chromatography to afford the title compound (1.63 g, 61%). After 2 h The reaction mixture is extracted with EtOAc the organic layer is washed with NaHCO3 and brine the washes are back-extracted once with EtOAc Then the combined organic layers are dried (MgSO4) filtered concentrated The crude compound is purified by flash column chromatography

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

Procedure: To a solution of diethyl 1H-pyrrolo[2,3-b]pyridine-2,6-dicarboxylate (Intermediate D, 1.00 g, 3.81 mmol) in DMF (15 mL) cooled to 0° C. is added 60% sodium hydride in mineral oil (168 mg, 4.19 mmol). The mixture is stirred at 0° C. for 20 min after which a solution of tert-butyl 6-methyl-1,2,3-oxathiazinane-3-carboxylate 2,2-dioxide (1.05 g, 4.19 mmol) in DMF (2 mL) is added. After being stirred overnight, the mixture is concentrated under reduced pressure and the residue is partitioned between ethyl acetate and saturated NaHCO3 solution. The layers are separated and the aqueous layer is further extracted with ethyl acetate. The combined organic phases are washed with brine, and are dried (Na2SO4). The solvent is removed in vacuo and the crude material is purified via flash column chromatography using a gradient elution of 0-30% ethyl acetate/heptanes to afford the title compound as a yellow oil (1.20 g, 73%). LCMS: 434.89 (M+H+). is added the mixture is concentrated under reduced pressure the residue is partitioned between ethyl acetate and saturated NaHCO3 solution The layers are separated the aqueous layer is further extracted with ethyl acetate The combined organic phases are washed with brine are dried (Na2SO4) The solvent is removed in vacuo the crude material is purified via flash column chromatography a gradient elution of 0-30% ethyl acetate/heptanes

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

Procedure: The crude tert-butyl 6-methyl-1,2,3-oxathiazinane-3-carboxylate 2-oxide (2.52 g, 10.7 mmol) is dissolved in acetonitrile (25 mL) and H2O (15 mL) is added. The solution is cooled in an ice bath and sodium periodate (3.4 g, 16.1 mmol) is added in one portion. After 5 min, the pH is adjusted to 7-8 by addition of saturated Na2HPO4 solution. Then RuCl3 (22 mg, 0.11 mmol) in H2O (0.5 mL) is added. The pH is kept between 6 and 9 by addition of Na2HPO4 solution. After 2 h, H2O (100 mL) is added and pH is adjusted to 6 by addition of 2M HCl solution. The reaction mixture is extracted with EtOAc and the organic layer is washed with NaHCO3 and brine and the washes are back extracted once with EtOAc. The combined organic layers are dried (MgSO4), filtered and concentrated. The crude product is purified via by flash column chromatography using a gradient elution of 5-80% ethyl acetate/hexanes which affords the title compound (1.63 g, 61%). The solution is cooled in an ice bath After 2 h The reaction mixture is extracted with EtOAc the organic layer is washed with NaHCO3 and brine the washes are back extracted once with EtOAc The combined organic layers are dried (MgSO4) filtered concentrated The crude product is purified via by flash column chromatography a gradient elution of 5-80% ethyl acetate/hexanes which