tert-butyl 3-cyanomorpholine-4-carboxylate

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

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

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl 3-cyanomorpholine-4-carboxylate (5 g, 23.6 mmol, the compound was synthesized according to the procedure as described in J. Med. Chem. 2007, 50(20), 4953-4975), sodium azide (1.53 g, 23.6 mmol) and ammonium chloride (0.63 g, 11.8 mmol) in anhydrous DMF (30 mL) was stirred at 100° C. for 72 hours and cooled to 25° C. The reaction mixture was diluted with EtOAc (300 mL), then washed with brine (150 mL×6). The organic phase was concentrated in vacuo and the residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=1/1) to give the title compound as a brownish solid (2.5 g, 41%). The compound was characterized by the following spectroscopic data: the compound was synthesized washed with brine (150 mL×6) The organic phase was concentrated in vacuo the residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=1/1)

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 (0.3 M) of tert-butyl 3-cyano-4-morpholinecarboxylate (prepared as described in the J. Med. Chem. 2007, 50, 4953-4975) in MeOH was added PtO2 (0.1 eq) and the mixture was stirred O/N under an H2 atmosphere at 50 psi. The reaction mixture was filtered and concentrated under reduced pressure to afford the title compound RR1. MS (ES) C10H20N2O3 required: 216, found: 217 (M+H)+. The reaction mixture was filtered concentrated under reduced pressure

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

Procedure: A solution of the product of Step 3 (1 eq.), hydroxylamine hydrochloride (1.4 eq.) and triethylamine (1.7 eq.) in EtOH (0.5 M) was refluxed under nitrogen for 5 hours. Mixture was concentrated and residues taken up in EtOAc and washed with water and brine. Combined organics were dried over Na2SO4 and evaporated giving the title compound as a yellow solid. Mixture was concentrated washed with water and brine Combined organics were dried over Na2SO4 evaporated

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

Procedure: A solution of the product of Step 2 (1 eq.) and triethylamine (2.1 eq.) in CH2Cl2 (0.1 M) was cooled to 0° C. and trifluoroacetic anhydride (1.1 eq.) added dropwise under nitrogen. Stirring was continued 3.5 hours more at room temperature and volatiles removed in vacuo. Residues taken in EtOAc were washed with water, brine and dried over Na2SO4. Evaporation gave the title compound as a brown solid. volatiles removed in vacuo were washed with water, brine dried over Na2SO4 Evaporation

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

Procedure: A solution of of the product of Step 3 (1 eq.), hydroxylamine hydrochloride (1.4 eq.) and triethylamine (1.7 eq.) in EtOH (0.5 M) was refluxed under nitrogen for 5 hours. Mixture was concentrated and residues taken up in EtOAc and washed with water and brine. Combined organics were dried over Na2SO4 and evaporated giving the title compound as a yellow solid. Mixture was concentrated washed with water and brine Combined organics were dried over Na2SO4 evaporated

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

Procedure: A solution of the product of Step 2 (1 eq.) and triethylamine (2.1 eq.) in CH2Cl2 (0.1 M) was cooled to 0° C. and trifluoroacetic anhydride (1.1 eq.) added dropwise under nitrogen. Stirring was continued 3.5 hours more at room temperature and volatiles removed in vacuo. Residues taken in EtOAc were washed with water, brine and dried over Na2SO4. Evaporation gave the title compound as a brown solid. volatiles removed in vacuo were washed with water, brine dried over Na2SO4 Evaporation

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

Procedure: A solution of of the product of Step 3 (1 eq.), hydroxylamine hydrochloride (1.4 eq.) and triethylamine (1.7 eq.) in EtOH (0.5 M) was refluxed under nitrogen for 5 hours. Mixture was concentrated and residues taken up in EtOAc and washed with water and brine. Combined organics were dried over Na2SO4 and evaporated giving the title compound as a yellow solid. Mixture was concentrated washed with water and brine Combined organics were dried over Na2SO4 evaporated

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

Procedure: A solution of the product of Step 2 (1 eq.) and triethylamine (2.1 eq.) in CH2Cl2 (0.1 M) was cooled to 0° C. and-trifluoroacetic anhydride (1.1 eq.) added dropwise under nitrogen. Stirring was continued 3.5 hours more at room temperature and volatiles removed in vacuo. Residues taken in EtOAc were washed with water, brine and dried over Na2SO4. Evaporation gave the title compound as a brown solid. volatiles removed in vacuo were washed with water, brine dried over Na2SO4 Evaporation