4-[tert-butyl(dimethyl)silyl]oxybutanal

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

Procedure: To CH2Cl2 (150 mL) at −78° C. were added oxalyl chloride (6.83 g, 53.8 mmol) and dry DMSO (8.41 g, 108 mmol), dropwise. After 5 min, 4-(tert-butyldimethylsilyloxy)butan-1-ol (10 g, 48.9 mmol) in CH2Cl2 (5 mL) was added dropwise. The mixture was stirred for an additional 30 min at −78° C., and Et3N (24.8 g, 245 mmol) was added. The mixture was then allowed to warm to room temperature over 30 min. After stirring for 3 hrs, 100 mL of water was added. The phases were separated, and the aqueous phase was extracted three times with 100 mL of diethyl ether. The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl. The organic layer was dried over MgSO4, and the solvent was removed under reduced pressure, to provide the title compound. to warm to room temperature over 30 min After stirring for 3 hrs The phases were separated the aqueous phase was extracted three times with 100 mL of diethyl ether The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl The organic layer was dried over MgSO4 the solvent was removed under reduced pressure

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

Procedure: To CH2Cl2 (150 mL) at −78° C. were added oxalyl chloride (6.83 g, 53.8 mmol) and dry DMSO (8.41 g, 108 mmol), dropwise. After 5 min, 4-(tert-butyldimethylsilyloxy)butan-1-ol (10 g, 48.9 mmol) in CH2Cl2 (5 mL) was added dropwise. The mixture was stirred for an additional 30 min at −78° C., and Et3N (24.8 g, 245 mmol) was added. The mixture was then allowed to warm to room temperature over 30 min. After stirring for 3 hrs, 100 mL of water was added. The phases were separated, and the aqueous phase was extracted three times with 100 mL of diethyl ether. The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl. The organic layer was dried over MgSO4, and the solvent was removed under reduced pressure, to provide the title compound. to warm to room temperature over 30 min After stirring for 3 hrs The phases were separated the aqueous phase was extracted three times with 100 mL of diethyl ether The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl The organic layer was dried over MgSO4 the solvent was removed under reduced pressure

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

Procedure: Using General Procedure B, reaction of (3,5-dimethyl-pyridin-2-yl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine, 4-(tert-butyl-dimethyl-silanyloxy)-butyraldehyde and NaBH(OAc)3 in CH2Cl2 gave [4-(tert-butyl-dimethyl-silanyloxy)-butyl]-(3,5-dimethyl-pyridin-2-yl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine.

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

Procedure: Using General Procedure B, reaction of (3,5-dimethyl-pyridin-2-yl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine, 4-(tert-butyl-dimethyl-silanyloxy)-butyraldehyde and NaBH(OAc)3 in CH2Cl2 gave [4-(tert-butyl-dimethyl-silanyloxy)-butyl]-(3,5-dimethyl-pyridin-2-yl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine.

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

Procedure: To CH2Cl2 (150 mL) at −78° C. were added oxalyl chloride (6.83 g, 53.8 mmol) and dry DMSO (8.41 g, 108 mmol), dropwise. After 5 min, 4-(tert-butyldimethylsilyloxy)butan-1-ol (10 g, 48.9 mmol) in CH2Cl2 (5 mL) was added dropwise. The mixture was stirred for an additional 30 min at −78° C., and Et3N (24.8 g, 245 mmol) was added. The mixture was then allowed to warm to room temperature over 30 min. After stirring for 3 hrs, 100 mL of water was added. The phases were separated, and the aqueous phase was extracted three times with 100 mL of diethyl ether. The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl. The organic layer was dried over MgSO4, and the solvent was removed under reduced pressure, to provide the title compound. to warm to room temperature over 30 min After stirring for 3 hrs The phases were separated the aqueous phase was extracted three times with 100 mL of diethyl ether The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl The organic layer was dried over MgSO4 the solvent was removed under reduced pressure

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

Procedure: Using General Procedure B, reaction of (3,5-dimethyl-pyridin-2-yl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine, 4-(tert-butyl-dimethyl-silanyloxy)-butyraldehyde and NaBH(OAc)3 in CH2Cl2 gave [4-(tert-butyl-dimethyl-silanyloxy)-butyl]-(3,5-dimethyl-pyridin-2-yl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine.

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

Procedure: To CH2Cl2 (150 mL) at −78° C. were added oxalyl chloride (6.83 g, 53.8 mmol) and dry DMSO (8.41 g, 108 mmol), dropwise. After 5 min, 4-(tert-butyldimethylsilyloxy)butan-1-ol (10 g, 48.9 mmol) in CH2Cl2 (5 mL) was added dropwise. The mixture was stirred for an additional 30 min at −78° C., and Et3N (24.8 g, 245 mmol) was added. The mixture was then allowed to warm to room temperature over 30 min. After stirring for 3 hrs, 100 mL of water was added. The phases were separated, and the aqueous phase was extracted three times with 100 mL of diethyl ether. The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl. The organic layer was dried over MgSO4, and the solvent was removed under reduced pressure, to provide the title compound. to warm to room temperature over 30 min After stirring for 3 hrs The phases were separated the aqueous phase was extracted three times with 100 mL of diethyl ether The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl The organic layer was dried over MgSO4 the solvent was removed under reduced pressure

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

Procedure: To CH2Cl2 (150 mL) at −78° C. were added oxalyl chloride (6.83 g, 53.8 mmol) and dry DMSO (8.41 g, 108 mmol), dropwise. After 5 min, 4-(tert-butyldimethylsilyloxy)butan-1-ol (10 g, 48.9 mmol) in CH2Cl2 (5 mL) was added dropwise. The mixture was stirred for an additional 30 min at −78° C., and Et3N (24.8 g, 245 mmol) was added. The mixture was then allowed to warm to room temperature over 30 min. After stirring for 3 hrs, 100 mL of water was added. The phases were separated, and the aqueous phase was extracted three times with 100 mL of diethyl ether. The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl. The organic layer was dried over MgSO4, and the solvent was removed under reduced pressure, to provide the title compound. to warm to room temperature over 30 min After stirring for 3 hrs The phases were separated the aqueous phase was extracted three times with 100 mL of diethyl ether The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl The organic layer was dried over MgSO4 the solvent was removed under reduced pressure

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

Procedure: Ethyl 2-(ethoxy(ethoxymethyl)phosphoryl)acetate (75.8 g, 0.3386 mol) was added to NaH (13.5 g, 60%) in 600 mL THF at 0° C., and the solution was warmed at RT for 1 hour, followed by the addition of 4-(tert-butyldimethylsilyloxy)butanal (5) (57.0 g, 0.2822 mol) in THF (200 mL) at 0° C., The mixture was stirred at RT for 2 hours. After removal of the solvent, the residue was dissolved in DCM, and the mixture was washed with water (3×200 mL) and brine (3×200 mL), dried over Na2SO4 and concentrated to give the desired compound of (E)-ethyl 6-(tert-butyldimethylsilyloxy)hex-2-enoate (7) (37.0 g, yield 48%) as yellow oil which was purified by column chromatography on silica gel (eluent: PE:EA=30:1). 1H NMR (300 MHz, CDCl3): δ 0.0021 (S, 6H), 0.0857 (S, 9H), 1.197 (t, 3H), 1.600 (m, 2H), 1.197 (t, 3H), 2.240 (q, 2H), 3.586 (t, 2H), 4.098 (q, 2H), 5.832 (d, J=15.6 Hz, 1H), 6.936-6.885 (m, 1H); LC-MS found 273 (M+H)+. After removal of the solvent the residue was dissolved in DCM the mixture was washed with water (3×200 mL) and brine (3×200 mL) dried over Na2SO4 concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of PCC (161.5 g, 0.75 mol) in DCM (1000 mL) was added 4-(tert-butyl dimethylsilyl oxy)butan-1-ol (102.0 g, 0.5 mol) in 500 mL of DCM, the mixture was stirred for about 1 hr at 0° C., then was warmed to RT and stirred for 2 hours. Then the mixture was filtered and the filtrate was concentrated in vacuo to give the desired compound of 4-(tert-butyldimethylsilyloxy)butanal (5) (121.2 g, yield 60%) as yellow oil which was purified by column chromatography on silica gel (eluent: PE:EA=50:1). 1H NMR (300 MHz, CDCl3): δ 0.04 (S, 6H), 0.0854 (S, 9H), 1.747 (m, 2H), 3.595 (d, J=12 Hz, 1H), 9.677 (d, J=3.3 Hz, 1H); LC-MC found 203 (M+H)+. was warmed to RT stirred for 2 hours Then the mixture was filtered the filtrate was concentrated in vacuo

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

Procedure: Using General Procedure B, reaction of (3,5-dimethyl-pyridin-2-yl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine, 4-(tert-butyl-dimethyl-silanyloxy)-butyraldehyde and NaBH(OAc)3 in CH2Cl2 gave [4-(tert-butyl-dimethyl-silanyloxy)-butyl]-(3,5-dimethyl-pyridin-2-yl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine.

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

Procedure: To CH2Cl2 (150 mL) at −78° C. were added oxalyl chloride (6.83 g, 53.8 mmol) and dry DMSO (8.41 g, 108 mmol), dropwise. After 5 min, 4-(tert-butyldimethylsilyloxy)butan-1-ol (10 g, 48.9 mmol) in CH2Cl2 (5 mL) was added dropwise. The mixture was stirred for an additional 30 min at −78° C., and Et3N (24.8 g, 245 mmol) was added. The mixture was then allowed to warm to room temperature over 30 min. After stirring for 3 hrs, 100 mL of water was added. The phases were separated, and the aqueous phase was extracted three times with 100 mL of diethyl ether. The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl. The organic layer was dried over MgSO4, and the solvent was removed under reduced pressure, to provide the title compound. to warm to room temperature over 30 min After stirring for 3 hrs The phases were separated the aqueous phase was extracted three times with 100 mL of diethyl ether The combined organic phases were washed successively with 50 mL of aqueous 1% HCl, 50 mL of water, 50 mL of aqueous 5% NaHCO3 and 50 mL of saturated aqueous NaCl The organic layer was dried over MgSO4 the solvent was removed under reduced pressure