Reagents:
Equipment and glassware:
Step 1. Phenylacetone (P2P) reductive amination.
Step 2. Benzyl group removing from N-benzylamphetamine (debenzylation).
Pd/C catalyst
- Phenylacetone (cas 103-79-7) 1000 g;
- (S)-(−)-α-Methylbenzylamine (cas 2627-86-3) 904 g;
- Sodium borhydride 282 g;
- Boric acid (H3BO3) 461 g (or p-toluenesulfonic acid monohydrate 1418 g, or benzoic acid 911 g);
- Sodium bicarbonate (NaHCO3);
- Sodium sulphate (Na2SO4) anhydrous;
- Formic acid 1026 g;
- Potassium hydroxide (KOH) 1251 g;
- Ethanol (EtOH) L;
- Palladium on carbon (Pd/C 10%) 475 g;
- Acetone 3 L;
- Sulfuric acid (H2SO4 98%) concentrated ~750 ml;
Equipment and glassware:
- 5 L Round bottom flask;
- Top stirrer and heating plate;
- Water bath;
- Glass rod and spatula;
- Rotovap machine (optional);
- Laboratory scale (1-1000 g is suitable);
- Measuring cylinders 100 and 500 mL;
- 1000 mL x3; 2000 mL x3; 500 mL x3 Beakers;
- 5 L Separatory funnel;
- Boiling chips;
- Buchner flask and funnel [Schott filter may be used for small quantities];
- Pasteur pipette;
- Freezer;
- Vacuum desiccator (optional);
Step 1. Phenylacetone (P2P) reductive amination.
1. Phenylacetone 1000 g and (S)-(−)-α-Methylbenzylamine 904 g are put into a 5 L round bottom flask;
2. The mixture is stirred at room temperature for 10-15 min;
3. Sodium borhydride 282 g is added slowly in several portions to the reaction mixture;
4. Then, boric acid (H3BO3) 461 g is added. It can be replaced by p-toluenesulfonic acid monohydrate 1418 g or benzoic acid 911 g;
5. The reaction mixture is stirred for 1 h at room temperature;
6. Next, the mixture is quenched with sodium bicarbonate (NaHCO3) saturated aqueous solution to alkaline pH 11-12;
7. Alkaline solution is extracted with dichloromethane (CH2Cl2) (or ether, or petroleum ether) 700 ml x3 in separatory funnel;
8. Extract is dried over anhydrous sodium sulphate (Na2SO4), filtered and concentrated under vacuum (optional) to get N-benzylamphetamine free base;
2. The mixture is stirred at room temperature for 10-15 min;
3. Sodium borhydride 282 g is added slowly in several portions to the reaction mixture;
4. Then, boric acid (H3BO3) 461 g is added. It can be replaced by p-toluenesulfonic acid monohydrate 1418 g or benzoic acid 911 g;
5. The reaction mixture is stirred for 1 h at room temperature;
6. Next, the mixture is quenched with sodium bicarbonate (NaHCO3) saturated aqueous solution to alkaline pH 11-12;
7. Alkaline solution is extracted with dichloromethane (CH2Cl2) (or ether, or petroleum ether) 700 ml x3 in separatory funnel;
8. Extract is dried over anhydrous sodium sulphate (Na2SO4), filtered and concentrated under vacuum (optional) to get N-benzylamphetamine free base;
Step 2. Benzyl group removing from N-benzylamphetamine (debenzylation).
1. Formic acid 1026 g, potassium hydroxide (KOH) 1251 g, N-benzylamphetamine free base 1000 g and ethanol (EtOH) 5 l are added into a 20 L flask, which is equipped with reflux condenser.
2. The reaction mixture is heated to a reflux temperature.
3. Palladium on carbon Pd/C 10% 475 g catalyst is added to the heated reaction mixture.
2. The reaction mixture is heated to a reflux temperature.
3. Palladium on carbon Pd/C 10% 475 g catalyst is added to the heated reaction mixture.
Pd/C catalyst
4. The mixture is stirred at reflux temperature for 60 min.
5. The mixture is cooled to room temperature and filtered after reaction procedure.
6. Ethanol solution is evaporated under vacuum (optional) to get dextroamphetamine free base oil.
7. The catalyst powder is collected on the filter, washed with distilled water twice and washed with ethanol once.
8. An isolated catalyst is dried and used in a next batch.
Step 3. Dextroamphetamine sulphate preparation.
1. Amphetamine free base from Step 2.6 is dissolved in acetone 2 l and stirred well.
2. Sulfuric acid (H2SO4) is added dropwise to reach pH 6.
5. The mixture is cooled to room temperature and filtered after reaction procedure.
6. Ethanol solution is evaporated under vacuum (optional) to get dextroamphetamine free base oil.
7. The catalyst powder is collected on the filter, washed with distilled water twice and washed with ethanol once.
8. An isolated catalyst is dried and used in a next batch.
Step 3. Dextroamphetamine sulphate preparation.
1. Amphetamine free base from Step 2.6 is dissolved in acetone 2 l and stirred well.
2. Sulfuric acid (H2SO4) is added dropwise to reach pH 6.
3. The mixture is put into a freezer for 12 h.
4. After that, the mixture is filtered and washed on a Buchner filter with cold acetone and dried on air or in vacuum desiccator to get Dextroamphetamine sulfate powder.
4. After that, the mixture is filtered and washed on a Buchner filter with cold acetone and dried on air or in vacuum desiccator to get Dextroamphetamine sulfate powder.
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