2-(CBZ-氨基)乙醛缩二甲醇

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Benzyl chloroformate (231.3 g, 1.3 mol) was added gradually to a mixture of aminoacetaldehyde dimethyl acetal (152.0 g, 1.3 mol) in toluene (750 mL) and aqueous NaOH (72.8 g, 1.82 mol; in 375 mL of water) at 10-20° C. After the addition was completed, the mixture was stirred at ambient temperature over 4 hours. The organic layer was separated, washed with brine (2×100 mL) and concentrated to provide the title compound as an oil (281.5 g, 90% yield). 1H NMR (CDCl4, 300 MHz) δ3.33 (t, J=6.0 Hz, 2H), 3.39 (s, 6H), 4.37 (t, J=6.0 Hz, 1H), 5.11 (s, 2H), 7.30 (m, 5H); MS (DCI/NH3) m/z 257 (M+NH4)+, 340 (M+H)+. After the addition The organic layer was separated washed with brine (2×100 mL) concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of benzyl N-(2,2-dimethoxyethyl)carbamate (50 g, 208.9 mmol) in toluene (180 mL) is treated with solid potassium hydroxide (51.6 g, 919.69 mmol) under nitrogen. After 10 minutes, benzyltriethylammonium chloride (0.8 g, 3.1 mmol) is added. After another 10 minutes a solution of allyl bromide (33 g, 272.8 mmol) in toluene (50 mL) is added drop wise over 10 minutes. The resultant mixture is stirred at 50° C. for 48 hours. The mixture is cooled to room temperature and quenched with water. The organic layer is separated, washed with brine, dried over magnesium sulfate, and concentrated to dryness to give the title compound (44 g, 75%). ES/MS (m/e): 280 (M+H). quenched with water The organic layer is separated washed with brine dried over magnesium sulfate concentrated to dryness

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of aminoacetaldehyde dimethyl acetal (25 mL, 229 mmol) in toluene (120 mL) is treated at 0° C. with a 4.85 M sodium hydroxide solution (70.8 mL, 343.5 mmol). The mixture is stirred at 0° C. for 10 minutes and benzyl chloroformate (33.8 mL, 229 mmol) is added keeping the internal temperature below 20° C. during the addition. The mixture is warmed to room temperature over 4 hours. The organic layer is separated, washed with brine, dried over sodium sulfate, and concentrated to dryness to give the title compound (54 g, 98%). ES/MS (m/e): 240 (M+H). the internal temperature below 20° C. during the addition The mixture is warmed to room temperature over 4 hours The organic layer is separated washed with brine dried over sodium sulfate concentrated to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Benzyl chloroformate (Aldrich, 231.3 g, 1.3 mol) was added gradually to a mixture of aminoacetaldehyde dimethyl acetal (Aldrich, 152.0 g, 1.3 mol) in toluene (750 mL) and aqueous NaOH (72.8 g, 1.82 mol; in 375 mL of water) at 10-20° C. After the addition was complete, the mixture was stirred at ambient temperature for 4 h. The layers were separated and the organic layer was washed with brine (2×100 mL) and concentrated under reduced pressure to provide the title compound as an oil (281.5 g, 90% yield). 1H NMR (CDCl4, 300 MHz) δ 3.33 (t, J=6.0 Hz, 2H), 3.39 (s, 6H), 4.37 (t, J=6.0 Hz, 1H), 5.11 (s, 2H), 7.30 (m, 5H); MS (DCl/NH3) m/z 257 (M+NH4)+, 240 (M+H)+. After the addition The layers were separated the organic layer was washed with brine (2×100 mL) concentrated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Benzyl chloroformate (Aldrich, 231.3 g, 1.3 mol) was added gradually to a mixture of aminoacetaldehyde dimethyl acetal (Aldrich, 152.0 g, 1.3 mol) in toluene (750 mL) and aqueous NaOH (72.8 g, 1.82 mol; in 375 mL of water) at 10-20° C. After the addition was complete, the mixture was stirred at ambient temperature for 4 h. The layers were separated and the organic layer was washed with brine (2×100 mL) and concentrated under reduced pressure to provide the title compound as an oil (281.5 g, 90% yield). 1H NMR (CDCl4, 300 MHz) δ 3.33 (t, J=6.0 Hz, 2H), 3.39 (s, 6H), 4.37 (t, J=6.0 Hz, 1H), 5.11 (s, 2H), 7.30 (m, 5H); MS (DCl/NH3) m/z 257 (M+NH4)+, 240 (M+H)+. After the addition The layers were separated the organic layer was washed with brine (2×100 mL) concentrated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Benzyl chloroformate (231.3 g, 1.3 mol) was added gradually to a mixture of aminoacetaldehyde dimethyl acetal (152.0 g, 1.3 mol) in toluene (750 mL) and aqueous NaOH (72.8 g, 1.82 mol; in 375 mL of water) at 10-20° C. After the addition was complete, the mixture was stirred at ambient temperature for 4 h. The organic layer was separated, washed with brine (2×100 mL) and concentrated to provide the title compound. MS (DCl/NH3): m/z 240 (M+1)+, 257 (M+18)+. After the addition The organic layer was separated washed with brine (2×100 mL) concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Benzyl chloroformate (231.3 g, 1.3 mol) was added gradually to a mixture of aminoacetaldehyde dimethyl acetal (152.0 g, 1.3 mol) in toluene (750 mL) and aqueous NaOH (72.8 g, 1.82 mol; in 375 mL of water) at 10-20° C. After the addition was complete, the mixture was stirred at ambient temperature for 4 h. The organic layer was separated, washed with brine (2×100 mL) and concentrated to provide the title compound. MS (DCl/NH3): m/z 240 (M+1)+, 257 (M+18)+. After the addition The organic layer was separated washed with brine (2×100 mL) concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Benzyl chloroformate (231.3 g, 1.3 mol) was added gradually to a mixture of aminoacetaldehyde dimethyl acetal (152.0 g, 1.3 mol) in toluene (750 mL) and aqueous NaOH (72.8 g, 1.82 mol; in 375 mL of water) at 10–20° C. After the addition was completed, the mixture was stirred at ambient temperature about 4 hours. The organic layer was separated, washed with brine (2×100 mL) and concentrated to provide the title compound. 1H NMR (CDCl3, 300 MHz) δ 3.33 (t, J=6.0 Hz, 2H), 3.39 (s, 6H), 4.37 (t, J=6.0 Hz, 1H), 5.11 (s, 2H), 7.30 (m, 5H); MS (DCI/NH3) m/z 257 (M+NH4)+, 240 (M+H)+. After the addition The organic layer was separated washed with brine (2×100 mL) concentrated

反应条件: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The solution of Example 4A in toluene (343 Kg) was charged to a 200-gallon reactor followed by addition of allyl bromide (41.5 Kg) and methyltributylammonium chloride (8.3 Kg). The mixture was stirred for 15 minutes, cooled to 16° C., and treated with 50% NaOH solution (296.9 Kg) slowly over 1 hour while maintaining the internal temperature below 30° C. The mixture was stirred at room temperature until there remained no more than 1.0% 1, as determined by HPLC. The mixture was allowed to settle and the layers were separated. The organic layer was washed with phosphate buffer solution made of 10 mM KH2PO4 and 10 mM K2HPO4 (2×260 Kg), followed by a water wash (256 Kg). while maintaining the internal temperature below 30° C The mixture was stirred at room temperature until there the layers were separated The organic layer was washed with phosphate buffer solution wash (256 Kg)