(s)-2-(dibenzylamino)-3-phenylpropanal

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

Procedure: Add sec-butyllithium (2.9 mL, 2.1 mmol) dropwise to a solution of freshly distilled (−)-sparteine (1 mL, 4.3 mmol) in diethyl ether (25 mL) over 3 min at −78° C. Add 2,2-dimethylpyrrolidine-1-carboxylic acid tert-butyl ester (645 mg, 3.2 mmol) in diethyl ether (2 mL) dropwise over 10 min. Stir 2 h, add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (967 mg, 2.9 mmol) in diethyl ether (2 mL) over 5 min and stir 20 min. Add saturated aqueous ammonium chloride solution and ethyl acetate and let warm to room temperature, separate the layers, extract the aqueous layer with ethyl acetate, wash the organic layer with saturated aqueous sodium chloride solution, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate) to give the title compound as a colorless oil (182 mg, 12%). stir 20 min separate the layers extract the aqueous layer with ethyl acetate wash the organic layer with saturated aqueous sodium chloride solution dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate)

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

Procedure: Add sec-butyllithium (2.9 mL, 2.1 mmol) dropwise to a solution of freshly distilled (−)-sparteine (1 mL, 4.3 mmol) in diethyl ether (25 mL) over 3 min at −78° C. Add 2,2-dimethylpyrrolidine-1-carboxylic acid tert-butyl ester (645 mg, 3.2 mmol) in diethyl ether (2 mL) dropwise over 10 min. Stir 2 h, add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (967 mg, 2.9 mmol) in diethyl ether (2 mL) over 5 min and stir 20 min. Add saturated aqueous ammonium chloride solution and ethyl acetate and let warm to room temperature, separate the layers, extract the aqueous layer with ethyl acetate, wash the organic layer with saturated aqueous sodium chloride solution, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate) to give the title compound as a colorless oil (182 mg, 12%). stir 20 min separate the layers extract the aqueous layer with ethyl acetate wash the organic layer with saturated aqueous sodium chloride solution dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate)

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

Procedure: Add sec-butyllithium (1.29 mL, 1.8 mmol) dropwise to a solution of (−)-sparteine (0.44 mL, 1.36 mmol) in diethyl ether (10 mL) over 3 min at −78° C. Add N-Boc-pyrrolidine (0.245 mL, 1.4 mmol) in diethyl ether (2 mL) dropwise over 10 min. Stir 2 h, add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (0.69 g, 2.1 mmol) in diethyl ether (1.8 mL) over 5 min and stir 20 min. Add acetic acid (0.16 mL) and warn to room temperature. Add saturated aqueous sodium chloride (20 mL), separate layers, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a foam (0.421 g, 60%). stir 20 min warn to room temperature Add saturated aqueous sodium chloride (20 mL), separate layers dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with hexanes and ethyl acetate)

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

Procedure: Add sec-butyllithium (1.29 mL, 1.8 mmol) dropwise to a solution of (−)-sparteine (0.44 mL, 1.36 mmol) in diethyl ether (10 mL) over 3 min at −78° C. Add N-Boc-pyrrolidine (0.245 mL, 1.4 mmol) in diethyl ether (2 mL) dropwise over 10 min. Stir 2 h, add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (0.69 g, 2.1 mmol) in diethyl ether (1.8 mL) over 5 min and stir 20 min. Add acetic acid (0.16 mL) and warn to room temperature. Add saturated aqueous sodium chloride (20 mL), separate layers, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a foam (0.421 g, 60%). stir 20 min warn to room temperature Add saturated aqueous sodium chloride (20 mL), separate layers dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with hexanes and ethyl acetate)

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

Procedure: Dissolve 2-(S)-dibenzylamino-3-phenylpropan-1-ol (5.00 g, 15.08 mmol) in dimethylsulfoxide (DMSO) (15 mL) and cool in an ice bath. Add triethylamine (8.4 mL, 60.0 mmol) followed by sulfur trioxide-pyridine complex (4.80 g, 30.2 mmol). Stir 30 min then slowly add water (15 mL). Dilute with ethyl acetate and wash with 5% aqueous citric acid (3×), saturated aqueous sodium chloride, dry (magnesium sulfate) and concentrate to give the title compound as a light yellow residue. cool in an ice bath wash with 5% aqueous citric acid (3×), saturated aqueous sodium chloride dry (magnesium sulfate) concentrate

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cool to −10° C. a well stirred mixture of O-allyl-N-(9-anthracenylmethyl)-cinchonidinium bromide (0.480 g, 0.8 mmol), potassium fluoride (3 gr, 51 mmol), THF (150 mL) and 5-nitropent-1-ene (2.34 g, 20 mmol) and treat with a solution of (S)-2-dibenzylamino-3-phenylpropionaldehyde (2.640 gr, 8 mmol). Allow mixture to warn to room temperature and stir for two days. Concentrate under reduced pressure. Purify on silica gel with hexane/ethyl ether mixtures to give a mixture of two products (2.7 g, 75%). to warn to room temperature stir for two days Concentrate under reduced pressure Purify on silica gel with hexane/ethyl ether to give

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve commercially available tert-butyl 4-benzyl-1-piperazinecarboxylate (2.9 g, 10.4 mmol) in diethyl ether (75 mL) under argon and cool to −78° C. Add tetramethylethylene diamine (1. 8 mL, 11.7 mmol) and sec-butyllithium (9 mL, 11.7 mmol) dropwise at −78° C. React for 1.5 h and add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (2.6 g, 7.9 mmol) in diethyl ether (18 mL) dropwise over 10 min. Stir for 45 min. Add saturated aqueous ammonium chloride solution and ethyl acetate and let warm to room temperature, separate the layers, extract the aqueous layer with ethyl acetate, wash the organic layer with saturated aqueous sodium chloride solution, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate) to give the title compound (the first spot to elute) as a white solid (1.45 g, 30%) and a second diastereomer (the second spot to elute) as a white solid (1.1 g, 23%). dropwise at −78° C React for 1.5 h separate the layers extract the aqueous layer with ethyl acetate wash the organic layer with saturated aqueous sodium chloride solution dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate)

Conditions: temp:-35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add N,N,N′,N′-tetrametlhylethylenediamine (1.4 mL, 9.11 mmol), then sec-butyllithium (1.4 M in cyclohexane, 7.2 mL, 10.1 mmol) to 2-ethylpiperidine-1-carboxylic acid tert-butyl ester in diethyl ether (18 mL) at −78° C. under a nitrogen atmosphere. Warm to −35° C. and stir for 1 h. Cool to −78° C. and add (2S)-2-(dibenzylamino)-3-phenylpropanal (3.0 g, 9.11 mmol) in diethyl ether (4 mL) and stir for 30 min. Quench at −78° C. with water, warm to room temperature and extract with diethyl ether. Combine the organic layers, dry (magnesium sulfate) and concentrate. Separate the two major diastereomers of 2-((2S)-2-dibenzylaniino-1-hydroxy-3-phenylpropyl)-6-ethylpiperidine-1-carboxylic acid tert-butyl ester using normal-phase preparative HPLC (Kromasil Si 60, 10 μm, 80×180 mm; 98:2 Hexane:Acetone; 130 mL/min). Add N,N,N′,N′-tetrametlhylethylenediamine (1.4 mL, 9.11 mmol) at −78° C. Cool to −78° C. stir for 30 min Quench at −78° C. with water warm to room temperature extract with diethyl ether dry (magnesium sulfate) concentrate Separate the two major diastereomers of 2-((2S)-2-dibenzylaniino-1-hydroxy-3-phenylpropyl)-6-ethylpiperidine-1-carboxylic acid tert-butyl ester using normal-phase preparative HPLC (Kromasil Si 60, 10 μm, 80×180 mm; 98:2 Hexane:Acetone; 130 mL/min)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 2-bromopyridine (2.73 mL, 28.63 mmol) in THF (150 mL) and cool to −78° C. Add n-butyllithium (12.0 mL, 2.5 M in hexanes). Slowly add 2-(S)-dibenzylamino-3-phenyl-propionaldehyde (4.71 g, 14.31 mmol) in THF (15 mL) and stir 30 min. Quench reaction with saturated aqueous ammonium chloride. Remove cold bath and warm to room temperature. Wash organic layer twice with 5% aqueous citric acid, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with dichloromethane and ethyl acetate) to give the title compound as a residue (3.654 g, 62%). Quench reaction with saturated aqueous ammonium chloride Remove cold bath warm to room temperature Wash organic layer twice with 5% aqueous citric acid, saturated aqueous sodium chloride, dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with dichloromethane and ethyl acetate)

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

Procedure: Dissolve 2-(S)-dibenzylamino-3-phenylpropan-1-ol (5.00 g, 15.08 mmol) in DMSO (15 mL) and cool in an ice bath. Add triethylamine (8.4 mL, 60.0 mmol) followed by sulfur trioxide-pyridine complex (4.80 g, 30.2 mmol), stir 30 min then slowly add water (15 mL). Dilute with ethyl acetate and wash with 5% aqueous citric acid (3×), saturated aqueous sodium chloride, dry (magnesium sulfate) and concentrate to give the title compound as a light yellow residue. cool in an ice bath wash with 5% aqueous citric acid (3×), saturated aqueous sodium chloride dry (magnesium sulfate) concentrate

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

Procedure: Add sec-butyllithium (2.9 mL, 2.1 mmol) dropwise to a solution of freshly distilled (−)-sparteine (1 mL, 4.3 mmol) in diethyl ether (25 mL) over 3 min at −78° C. Add 2,2-dimethylpyrrolidine-1-carboxylic acid tert-butyl ester (645 mg, 3.2 mmol) in diethyl ether (2 mL) dropwise over 10 min. Stir 2 h, add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (967 mg, 2.9 mmol) in diethyl ether (2 mL) over 5 min and stir 20 min. Add saturated aqueous ammonium chloride solution and ethyl acetate and let warm to room temperature, separate the layers, extract the aqueous layer with ethyl acetate, wash the organic layer with saturated aqueous sodium chloride solution, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate) to give the title compound as a colorless oil (182 mg, 12%). stir 20 min separate the layers extract the aqueous layer with ethyl acetate wash the organic layer with saturated aqueous sodium chloride solution dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with 4:1 hexanes:ethyl acetate)

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

Procedure: Add sec-butyllithium (1.29 mL, 1.8 mmol) dropwise to a solution of (−)-sparteine (0.44 mL, 1.36 mmol) in diethyl ether (10 mL) over 3 min at −78° C. Add N-Boc-pyrrolidine (0.245 mL, 1.4 mmol) in diethyl ether (2 mL) dropwise over 10 min. Stir 2 h, add 2-(S)-dibenzylamino-3-phenylpropionaldehyde (0.69 g, 2.1 mmol) in diethyl ether (1.8 mL) over 5 min and stir 20 min. Add acetic acid (0.16 mL) and warn to room temperature. Add saturated aqueous sodium chloride (20 mL), separate layers, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a foam (0.421 g, 60%). stir 20 min warn to room temperature Add saturated aqueous sodium chloride (20 mL), separate layers dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with hexanes and ethyl acetate)