4,4-diethoxybutan-1-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 35.8 g (0.2 mol) of 4-aminobutyraldehyde-diethylacetal (90%) are dissolved in 600 ml of dichloromethane, 300 ml of saturated sodium hydrogen carbonate solution are added, and the mixture is cooled to 0° C. 17 ml (0.24 mol) of acetyl chloride are added dropwise at 0°-5° C., and the mixture is stirred for a further 6 hours at 0°-5° C. The organic phase is separated off and the aqueous phase is extracted twice more with dichloromethane. The organic phases are combined, dried over MgSO4, filtered and concentrated by evaporation in a rotary evaporator. The residue is purified by chromatography on silica gel with ethyl acetate. 4-(N-acetylamino)butyraldehyde-diethylacetal is obtained in the form of a yellowish oil. The organic phase is separated off the aqueous phase is extracted twice more with dichloromethane dried over MgSO4 filtered concentrated by evaporation in a rotary evaporator The residue is purified by chromatography on silica gel with ethyl acetate

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

Procedure: Methylvinyl ketone (18.0 g, 256 mmol) was added dropwise to a solution of the 4,4-diethoxybutylamine (24.8 g, 154 mmol) in diethyl ether at 0° C. and stirred for one hour. The reaction was allowed to warm to room temperature and stir for 2 hours. The reaction was poured into 350 ml of 2N hydrochloric acid and the layers were separated. The aqueous layer was heated on a steam bath for 1 hour and then allowed to stir at 40° C. for 18 hours. The reaction was made basic with a sodium hydroxide solution and then extracted with methylene chloride. The extracts were dried over sodium sulfate and concentrated to give 20 g of an orange oil. This oil was distilled in vacuo at 74-84° C./5 mmHg to give 6.68 g of racemic product. (31%). MS(FD) (m/e): 139. 1H-NMR. stir for 2 hours the layers were separated The aqueous layer was heated on a steam bath for 1 hour to stir at 40° C. for 18 hours extracted with methylene chloride The extracts were dried over sodium sulfate concentrated

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

Procedure: The methylvinyl ketone (18.0 g, 256 mmol) was added dropwise to a solution of the 4,4-diethoxybutylamine (24.8 g, 154 mmol) in diethyl ether at 0° C. and stirred for one hour. The reaction was allowed to warm to room temperature and stir for 2 hours. The reaction was poured into 350 ml of 2N hydrochloric acid and the layers were separated. The aqueous layer was heated on a steam bath for 1 hour and then allowed to stir at 40° C. for 18 hours. The reaction was made basic with a sodium hydroxide solution and then extracted with methylene chloride. The extracts were dried over sodium sulfate and concentrated to give 20 g of an orange oil. This oil was distilled in vacuo at 74°-84° C./5 mmHg to give 6.68 g of racemic product. (31%). MS(FD)(m/e): 139. stir for 2 hours the layers were separated The aqueous layer was heated on a steam bath for 1 hour to stir at 40° C. for 18 hours extracted with methylene chloride The extracts were dried over sodium sulfate concentrated

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

Procedure: Three portions of benzyl chloroformate (260 ml) in dichloromethane (170 ml) were added sequentially over 1 h 40 min to a vigorously stirred mixture of 4-aminobutyraldehyde diethyl acetal (910 ml) in dichloromethane (3 l ) and aqueous sodium carbonate (1M, 3 l). Stirring was continued for 50 min until gas evolution ceased. N-(2-aminoethyl)piperazine (40 ml) was added and stirring was continued for 1 h 15 min. The layers were separated and the organic layer was washed with aqueous citric acid (1M, 3.8 l) and saturated aqueous sodium bicarbonate (2 l), dried (MgSO4), filtered and concentrated in vacuo to give the title compound as a yellow oil (1.6 kg). T.l.c. (Ether) Rf 0.5. stirring was continued for 1 h 15 min The layers were separated the organic layer was washed with aqueous citric acid (1M, 3.8 l) and saturated aqueous sodium bicarbonate (2 l) dried (MgSO4) filtered concentrated in vacuo

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

Procedure: Methylvinyl ketone (18.0 g, 256 mmol) was added dropwise to a solution of the 4,4-diethoxybutylamine (24.8 g, 154 mmol) in diethyl ether at 0° C. and stirred for one hour. The reaction was allowed to warm to room temperature and stir for 2 hours. The reaction was poured into 350 ml of 2N hydrochloric acid and the layers were separated. The aqueous layer was heated on a steam bath for 1 hour and then allowed to stir at 40° C. for 18 hours. The reaction was made basic with a sodium hydroxide solution and then extracted with methylene chloride. The extracts were dried over sodium sulfate and concentrated to give 20 g of an orange oil. This oil was distilled in vacuo at 74-84° C./5 mmHg to give 6.68 g of racemic product. (31%). MS(FD)(m/e): 139. 1H-NMR. stir for 2 hours the layers were separated The aqueous layer was heated on a steam bath for 1 hour to stir at 40° C. for 18 hours extracted with methylene chloride The extracts were dried over sodium sulfate concentrated

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

Procedure: Methylvinyl ketone (18.0 g, 256 mmol) was added dropwise to a solution of the 4,4-diethoxybutylamine (24.8 g, 154 mmol) in diethyl ether at 0° C. and stirred for one hour. The reaction was allowed to warm to room temperature and stir for 2 hours. The reaction was poured into 350 ml of 2N hydrochloric acid and the layers were separated. The aqueous layer was heated on a steam bath for 1 hour and then allowed to stir at 40° C. for 18 hours. The reaction was made basic with a sodium hydroxide solution and then extracted with methylene chloride. The extracts were dried over sodium sulfate and concentrated to give 20 g of an orange oil. This oil was distilled in vacuo at 74-84° C./5 mmHg to give 6.68 g of racemic product. (31%). MS(FD)(m/e): 139. 1H-NMR. stir for 2 hours the layers were separated The aqueous layer was heated on a steam bath for 1 hour to stir at 40° C. for 18 hours extracted with methylene chloride The extracts were dried over sodium sulfate concentrated

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Aminobutyraldehyde diethyl acetal (AmBDA, 75 g, 1.09 mol, Aldrich Chemical) was combined with a two phase mixture of 955 mL of CH2Cl2 and 160 mL of 14 N NaOH in a 3 neck flask equipped with a thermometer and an efficient mechanical stirrer. This was cooled to 15° C. with an ice bath. Acryloyl chloride (98.3 g, 1.09 mol. Aldrich) was added via an addition funnel at a rate slow enough to maintain the reaction temperature below 30° C. Reaction monitoring by capillary glpc revealed essentially complete AmBDA consumption when the acryloyl chloride addition was complete. Agitation was continued for 1 h. The layers were separated (water may be added to dissolve precipitated salt and improve phase separation) and the organic phase was washed with saturated brine. The brine was combined with the aqueous layer and back extracted with CH2Cl2 . The combined organic layers were neutralized with saturated aqueous NaH2PO4, dried over anhydrous MgCl2 and concentrated on a rotary evaporator at 40° C. to give 99% pure ABDA (by glpc) in 87% yield. The product can be freed of any high molecular weight by-products by kugelrohr distillation (120°-125° C. at 0.2 torr), but this produces significant yield losses and partial isomerization to N-acryloyl-5-ethoxy pyrrolidine (AEP) and related products. The pot temperature should not exceed 60° C. during these operations. The yield loses are minimized by adding a basic reagent, such as Na2CO3 , and a radical inhibitor, such as methylene blue, to the distillation vessel. equipped with a thermometer and an efficient mechanical stirrer to maintain the reaction temperature below 30° C Reaction monitoring by capillary glpc AmBDA consumption when the acryloyl chloride addition The layers were separated (water may be added to dissolve precipitated salt and improve phase separation) the organic phase was washed with saturated brine back extracted with CH2Cl2 dried over anhydrous MgCl2 concentrated on a rotary evaporator at 40° C. to give 99% pure ABDA (by glpc) in 87% yield The product can be freed of any high molecular weight by-products by kugelrohr distillation (120°-125° C. at 0.2 torr)