(S)-4-tert-butyl 3-Methyl Morpholine-3,4-dicarboxylate

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

Procedure: A solution of example 1109C (522 mg, 2.0 mmol) in 4 mL of methylene chloride was cooled in an ice/acetone bath and triethylsilane (1.6 mL, 10.0 mmol) was added. The solution was then treated with a solution of boron trifluoride etherate (0.27 mL, 2.2 mmol) in 1 mL of methylene chloride. After stirring 30 minutes, the bath was removed and stirring continued for 30 minutes and the mixture was quenched by the addition of 2M aqueous sodium carbonate. The mixture was diluted with water and methylene choride and the layers separated. The aqueous layer was extracted with 2 portions of methylene chloride and the combined organic layers were dried, filtered and concentrated. The residue was purified by column chromatography on silica gel (40 g, 20% ethyl acetate/hexanes) to provide 200 mg (41%) of the title compound. MS (DCI, NH3): 246 (MH+); 263 (M+NH4)+. the bath was removed stirring continued for 30 minutes the mixture was quenched by the addition of 2M aqueous sodium carbonate The mixture was diluted with water and methylene choride the layers separated The aqueous layer was extracted with 2 portions of methylene chloride the combined organic layers were dried filtered concentrated The residue was purified by column chromatography on silica gel (40 g, 20% ethyl acetate/hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (S)-4-tert-butyl 3-methyl morpholine-3,4-dicarboxylate (0.93 g, 3.8 mmol) and 2-aminoethanol (5 g, 81.9 mmol) in methanol (2 mL) was stirred at 80° C. for 7 hours under N2. The mixture was concentrated in vacuo, diluted with EtOAc (100 mL) and acetic acid (5 mL). The organic layer was washed with brine (80 mL×6), dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to give the title compound as a white solid (0.8 g, 77%). The compound was characterized by the following spectroscopic data: The mixture was concentrated in vacuo diluted with EtOAc (100 mL) and acetic acid (5 mL) The organic layer was washed with brine (80 mL×6) dried over Na2SO4 filtered The filtrate was concentrated in vacuo

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (S)-4-tert-butyl 3-methyl morpholine-3,4-dicarboxylate (0.93 g, 3.8 mmol) and 2-aminoethanol (5 g, 81.9 mmol) in methanol (2 mL) was stirred at 80° C. for 7 hours under N2. The mixture was concentrated in vacuo, diluted with EtOAc (100 mL) and acetic acid (5 mL). The organic layer was washed with brine (80 mL×6), dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to give the title compound as a white solid (0.8 g, 77%). The compound was characterized by the following spectroscopic data: The mixture was concentrated in vacuo diluted with EtOAc (100 mL) and acetic acid (5 mL) The organic layer was washed with brine (80 mL×6) dried over Na2SO4 filtered The filtrate was concentrated in vacuo

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (S)-4-tert-butyl 3-methyl morpholine-3,4-dicarboxylate (0.93 g, 3.8 mmol) and 2-aminoethanol (5 g, 81.9 mmol) in methanol (2 mL) was stirred at 80° C. for 7 hours under N2. The mixture was concentrated in vacuo, diluted with EtOAc (100 mL) and acetic acid (5 mL). The organic layer was washed with brine (80 mL×6), dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to give the title compound as a white solid (0.8 g, 77%). The compound was characterized by the following spectroscopic data: The mixture was concentrated in vacuo diluted with EtOAc (100 mL) and acetic acid (5 mL) The organic layer was washed with brine (80 mL×6) dried over Na2SO4 filtered The filtrate was concentrated in vacuo

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

Procedure: A solution of example 1109C (522 mg, 2.0 mmol) in 4 mL of methylene chloride was cooled in an ice/acetone bath and triethylsilane (1.6 mL, 10.0 mmol) was added. The solution was then treated with a solution of boron trifluoride etherate (0.27 mL, 2.2 mmol) in 1 mL of methylene chloride. After stirring 30 minutes, the bath was removed and stirring continued for 30 minutes and the mixture was quenched by the addition of 2M aqueous sodium carbonate. The mixture was diluted with water and methylene choride and the layers separated. The aqueous layer was extracted with 2 portions of methylene chloride and the combined organic layers were dried, filtered and concentrated. The residue was purified by column chromatography on silica gel (40 g, 20% ethyl acetate/hexanes) to provide 200 mg (41%) of the title compound. MS (DCI, NH3): 246 (MH+); 263 (M+NH4)+. the bath was removed stirring continued for 30 minutes the mixture was quenched by the addition of 2M aqueous sodium carbonate The mixture was diluted with water and methylene choride the layers separated The aqueous layer was extracted with 2 portions of methylene chloride the combined organic layers were dried filtered concentrated The residue was purified by column chromatography on silica gel (40 g, 20% ethyl acetate/hexanes)