4-Benzyl-2,2-dimethylmorpholine

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

Procedure: Dissolve 4-benzyl-2,2-dimethyl-morpholine (5.67 g, 27.6 mmol) in CH2Cl2 (50 mL) and add 1-chloroethyl chloroformate (4.60 mL, 42.2 mmol) while stirring at room temperature. After 4 h, concentrate the solution and treat the residue with MeOH (60 mL). Heat the mixture at 60° C. for 2 h, then concentrate again. Dissolve the residue in water (125 mL) and wash with tert-butyl methyl ether (125 mL). Concentrate the aqueous layer and dry the resulting residue at 80° C. under vacuum to give the title compound (3.91 g, 93%) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.52 (2H, br s), 3.75 (2H, m), 2.89-2.96 (4H, m), 1.25 (6H, s). concentrate the solution treat the residue with MeOH (60 mL) Heat the mixture at 60° C. for 2 h concentrate again Dissolve the residue in water (125 mL) wash with tert-butyl methyl ether (125 mL) Concentrate the aqueous layer dry the resulting 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-dimethyl-morpholine (5.67 g, 27.6 mmol) in CH2Cl2 (50 mL) and add 1-chloroethyl chloroformate (4.60 mL, 42.2 mmol) while stirring at room temperature. After 4 h, concentrate the solution and treat the residue with MeOH (60 mL). Heat the mixture at 60° C. for 2 h, then concentrate again. Dissolve the residue in water (125 mL) and wash with tert-butyl methyl ether (125 mL). Concentrate the aqueous layer and dry the resulting residue at 80° C. under vacuum to give the title compound (3.91 g, 93%) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.52 (2H, br s), 3.75 (2H, m), 2.89-2.96 (4H, m), 1.25 (6H, s). concentrate the solution treat the residue with MeOH (60 mL) Heat the mixture at 60° C. for 2 h concentrate again Dissolve the residue in water (125 mL) wash with tert-butyl methyl ether (125 mL) Concentrate the aqueous layer dry the resulting residue at 80° C. under vacuum

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

Procedure: Add 2-[benzyl-(2-methyl-allyl)-amino]-ethanol (13.0 g, 63.2 mmol) to a slurry of mercury (It) acetate (20.7 g, 65.0 mmol) in water (45 mL) and THF (45 mL). After 3 h, treat the mixture with NaOH (25 mL, 2.5 M aqueous, 125 mmol) followed by NaBH4 (2.72 g, 71.9 mmol). After 19 h, decant the mixture away from the metallic mercury and add to a separatory funnel with tert-butyl methyl ether (250 mL). Separate the organic solution, wash with water (250 mL), filter through a silica plug, and concentrate. Purify the residue by flash chromatography using a gradient from 5% to 10% tert-butyl methyl ether in CH2Cl2. Collect and concentrate the fractions containing product then dissolve the residue in hexanes (100 mL). Filter the solution through Celite® to remove metallic mercury and then concentrate the filtrate to give the title compound (7.01 g, 54%) as a colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.20-7.40 (5H, m), 3.60 (2H, m), 3.42 (2H, s), 2.29 (2H, m), 2.10 (2H, s), 1.14 (6H, s). After 19 h decant the mixture away from the metallic mercury add to a separatory funnel with tert-butyl methyl ether (250 mL) Separate the organic solution wash with water (250 mL) filter through a silica plug concentrate Purify the residue by flash chromatography Collect concentrate the fractions containing product then dissolve the residue in hexanes (100 mL) Filter the solution through Celite® to remove metallic mercury concentrate the filtrate

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

Procedure: Dissolve 4-benzyl-2,2-dimethyl-morpholine (5.67 g, 27.6 mmol) in CH2Cl2 (50 mL) and add 1-chloroethyl chloroformate (4.60 mL, 42.2 mmol) while stirring at room temperature. After 4 h, concentrate the solution and treat the residue with MeOH (60 mL). Heat the mixture at 60° C. for 2 h, then concentrate again. Dissolve the residue in water (125 mL) and wash with tert-butyl methyl ether (125 mL). Concentrate the aqueous layer and dry the resulting residue at 80° C. under vacuum to give the title compound (3.91 g, 93%) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.52 (2H, br s), 3.75 (2H, m), 2.89-2.96 (4H, m), 1.25 (6H, s). concentrate the solution treat the residue with MeOH (60 mL) Heat the mixture at 60° C. for 2 h concentrate again Dissolve the residue in water (125 mL) wash with tert-butyl methyl ether (125 mL) Concentrate the aqueous layer dry the resulting residue at 80° C. under vacuum

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

Procedure: Add 2-[benzyl-(2-methyl-allyl)-amino]-ethanol (13.0 g, 63.2 mmol) to a slurry of mercury (It) acetate (20.7 g, 65.0 mmol) in water (45 mL) and THF (45 mL). After 3 h, treat the mixture with NaOH (25 mL, 2.5 M aqueous, 125 mmol) followed by NaBH4 (2.72 g, 71.9 mmol). After 19 h, decant the mixture away from the metallic mercury and add to a separatory funnel with tert-butyl methyl ether (250 mL). Separate the organic solution, wash with water (250 mL), filter through a silica plug, and concentrate. Purify the residue by flash chromatography using a gradient from 5% to 10% tert-butyl methyl ether in CH2Cl2. Collect and concentrate the fractions containing product then dissolve the residue in hexanes (100 mL). Filter the solution through Celite® to remove metallic mercury and then concentrate the filtrate to give the title compound (7.01 g, 54%) as a colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.20-7.40 (5H, m), 3.60 (2H, m), 3.42 (2H, s), 2.29 (2H, m), 2.10 (2H, s), 1.14 (6H, s). After 19 h decant the mixture away from the metallic mercury add to a separatory funnel with tert-butyl methyl ether (250 mL) Separate the organic solution wash with water (250 mL) filter through a silica plug concentrate Purify the residue by flash chromatography Collect concentrate the fractions containing product then dissolve the residue in hexanes (100 mL) Filter the solution through Celite® to remove metallic mercury concentrate the filtrate