2,2,6,6-tetramethylmorpholine

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

Procedure: Dissolve 500 mg (2.79 mmol) of 2,2,6,6-tetramethyl-morpholine (500 mg, 2.79 mmol) in dichloroethane (10 mL). Add benzyloxy-acetaldehyde (470 μl, 3.35 mmol) and stir at room temperature for 20 min. Add sodium triacetoxyborohydride (770 mg, 3.63 mmol) and continue stirring at room temperature for 20 h. Pour the reaction mixture into 100 mL of 1N NaOH (100 mL) and extract with CH2Cl2 (2×100 mL). Wash the combined organic layers with brine (100 mL). Purify using silica gel chromatography, using a gradient of 0% to 10% (2N NH3 in MeOH)/CHCl3 as eluent, to give 490 mg (63%) of the desired product. MS (ES+) 278.3 (M+1)+. extract with CH2Cl2 (2×100 mL) Wash the combined organic layers with brine (100 mL) Purify

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

Procedure: Dissolve 4-benzyl-2,2,6,6-tetramethylmorpholine (Bennett, G. B.; Houlihan, W. J.; Mason, R. B.; Engstrom, R. G. J. Med. Chem. 1976, 19, 709-714) (11.0 g, 47.1 mmol) in EtOH (650 mL) and add 3% Pd/C (8.61 g). Shake the mixture under hydrogen (60 psi) at 40° C. for 24 h. Filter the mixture to remove Pd catalyst, and treat the filtrate with 2M HCl in ether, then concentrate. Dry the residue at 80° C. under vacuum to give the title compound (6.79 g) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.8 (2H, br s), 2.88 (4H, s), 1.25 (12H, s). Filter the mixture to remove Pd catalyst treat the filtrate with 2M HCl in ether concentrate Dry the residue at 80° C. under vacuum

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

Procedure: Dissolve 4-benzyl-2,2,6,6-tetramethylmorpholine (Bennett, G. B.; Houlihan, W. J.; Mason, R. B.; Engstrom, R. G. J. Med. Chem. 1976, 19, 709-714) (11.0 g, 47.1 mmol) in EtOH (650 mL) and add 3% Pd/C (8.61 g). Shake the mixture under hydrogen (60 psi) at 40° C. for 24 h. Filter the mixture to remove Pd catalyst, and treat the filtrate with 2M HCl in ether, then concentrate. Dry the residue at 80° C. under vacuum to give the title compound (6.79 g) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.8 (2H, br s), 2.88 (4H, s), 1.25 (12H, s). Filter the mixture to remove Pd catalyst treat the filtrate with 2M HCl in ether concentrate Dry the residue at 80° C. under vacuum

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

Procedure: Dissolve 500 mg (2.79 mmol) of 2,2,6,6-tetramethyl-morpholine (500 mg, 2.79 mmol) in dichloroethane (10 mL). Add benzyloxy-acetaldehyde (470 μl, 3.35 mmol) and stir at room temperature for 20 min. Add sodium triacetoxyborohydride (770 mg, 3.63 mmol) and continue stirring at room temperature for 20 h. Pour the reaction mixture into 100 mL of 1N NaOH (100 mL) and extract with CH2Cl2 (2×100 mL). Wash the combined organic layers with brine (100 mL). Purify using silica gel chromatography, using a gradient of 0% to 10% (2N NH3 in MeOH)/CHCl3 as eluent, to give 490 mg (63%) of the desired product. MS (ES+) 278.3 (M+1)+. extract with CH2Cl2 (2×100 mL) Wash the combined organic layers with brine (100 mL) Purify

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

Procedure: Dissolve 4-benzyl-2,2,6,6-tetramethylmorpholine (Bennett, G. B.; Houlihan, W. J.; Mason, R. B.; Engstrom, R. G. J. Med. Chem. 1976, 19, 709-714) (11.0 g, 47.1 mmol) in EtOH (650 mL) and add 3% Pd/C (8.61 g). Shake the mixture under hydrogen (60 psi) at 40° C. for 24 h. Filter the mixture to remove Pd catalyst, and treat the filtrate with 2M HCl in ether, then concentrate. Dry the residue at 80° C. under vacuum to give the title compound (6.79 g) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.8 (2H, br s), 2.88 (4H, s), 1.25 (12H, s). Filter the mixture to remove Pd catalyst treat the filtrate with 2M HCl in ether concentrate Dry the residue at 80° C. under vacuum