Reaction scheme:
- 50 L Batch reactor, which is equipped with drip funnel, top stirrer, thermometer, temperature control system (cooling) and reflux condenser;
- 10 L Flask;
- Retort stand and clamp for securing apparatus (optional);
- Top stirrer;
- Heating plate;
- Funnel;
- Several buckets 25 L;
- Beaker 2000 mL;
- Pyrex dishes;
- Vacuum source;
- Scale;
- Measuring cylinder 1000 mL;
- Glass rod and spatula;
- Scoops;
- Nutsche filter;
- Rotary evaporator;
Reagents:
- Indole 1000 g, cas: 120-72-9;
- Dichloromethane (CH2Cl2) 15 liters, cas: 75-09-2;
- Tin (IV) chloride 2000 ml, cas: 7646-78-8;
- 1-Naphthoyl chloride 1627 g, cas: 879-18-5;
- Nitromethane 10 L, cas: 75-52-5;
- Ethyl acetate 15 L, cas: 141-78-6;
- Sodium hydroxide 1300 g, cas: 1310-73-2;
- TBAB 800 g, cas: 1643-19-2;
- 1-Bromopentane 1500 g, cas: 110-53-2;
- Distilled water 20 L;
- Magnesium sulphate (MgSO4);
Step 1. 3-(1-naphthoyl)indole (cas 109555-87-5) from 1-Naphthoyl chloride and Indole.
1. Tin (IV) chloride (SnCl4) 2000 ml is added in one portion to a indole 1000 g solution in 50 l batch reactor dichloromethane (CH2Cl2) 15 liters with a constant stirring and external cooling by a cold water bath or cold cooling system.
2. Than, reaction mixture is cooled to a room temperature and stirred for 30 min. Next, 1-naphthoyl chloride 1627 g is poured in small portions to the suspension, followed by nitromethane 10 L.
3. The mixture is stirred for 2 h at room temperature.
4. The reaction mixture is quenched with ice water 20 L, extracted with ethyl acetate 15 L and filtered to remove inorganic precipitates on a nutsche filter.
5. The organic phase is dried over Na2SO4 and MgSO4, filtered from solids and concentrated at reduced pressure to give the 3-(1-naphthoyl)indole (cas 109555-87-5) as a crystals.
Step 2. 1-pentyl-3-(1-naphthoyl)indole (JWH-018) from 3-(1-naphthoyl)indole (cas 109555-87-5).
2. Than, reaction mixture is cooled to a room temperature and stirred for 30 min. Next, 1-naphthoyl chloride 1627 g is poured in small portions to the suspension, followed by nitromethane 10 L.
3. The mixture is stirred for 2 h at room temperature.
4. The reaction mixture is quenched with ice water 20 L, extracted with ethyl acetate 15 L and filtered to remove inorganic precipitates on a nutsche filter.
5. The organic phase is dried over Na2SO4 and MgSO4, filtered from solids and concentrated at reduced pressure to give the 3-(1-naphthoyl)indole (cas 109555-87-5) as a crystals.
Step 2. 1-pentyl-3-(1-naphthoyl)indole (JWH-018) from 3-(1-naphthoyl)indole (cas 109555-87-5).
1. 3-(1-naphtoyl) indole 2000 g, sodium hydroxide (NaOH) 1300 g, TBAB 800 g are weighed and placed into a 10 L flask.
2. 1-Bromopentane 1500 g and distilled water 3000 ml are poured into the flask.
3. Reaction mixture is stirred until two layers are separated and solid sodium hydroxide is dissolved completely.
4. Sodium hydroxide dissolving is conducted with heat releasing, hence the mixture is self-heated.
5. The flask is put on heating plate and heated with maximum power after two layers are divided and all sodium hydroxide is dissolved.
6. Top stirrer is installed onto the flask. It is necessary to stir the solution well enough so that the layers are mixed in homogeneous mixture.
7. Top stirrer have to work with constant power during reaction.
8. The mixture is simmered until reaction solution is become milky and homogeneous. It takes 15-30 min.
9. Then, the flask is removed from heating plate and the mixture is separated into two layers.
10. Top layer is needed. The product is crystallized directly in the flask, which makes it difficult to take out. Therefore, procedures are done quickly.
11. Top layer is poured neatly into Pyrex dishes or silicone molds.
12. JWH-018 is left for 24 h in order to crystallization. Silicone molds are taken for convenient handling with JWH-018 product by reason that it is crystallized and taken a form, which it was poured.
13. Crystallized JWH-018 product is taken out and crushed. Then, It is air dried on a paper or a dish in a warm dry well ventilated room (better to use vacuum desiccator to significantly increase drying speed). Drying procedure depends on amount of JWH-018 product and takes ~48 h. Reaction yield is 3000 g.
2. 1-Bromopentane 1500 g and distilled water 3000 ml are poured into the flask.
3. Reaction mixture is stirred until two layers are separated and solid sodium hydroxide is dissolved completely.
4. Sodium hydroxide dissolving is conducted with heat releasing, hence the mixture is self-heated.
5. The flask is put on heating plate and heated with maximum power after two layers are divided and all sodium hydroxide is dissolved.
6. Top stirrer is installed onto the flask. It is necessary to stir the solution well enough so that the layers are mixed in homogeneous mixture.
7. Top stirrer have to work with constant power during reaction.
8. The mixture is simmered until reaction solution is become milky and homogeneous. It takes 15-30 min.
9. Then, the flask is removed from heating plate and the mixture is separated into two layers.
10. Top layer is needed. The product is crystallized directly in the flask, which makes it difficult to take out. Therefore, procedures are done quickly.
11. Top layer is poured neatly into Pyrex dishes or silicone molds.
12. JWH-018 is left for 24 h in order to crystallization. Silicone molds are taken for convenient handling with JWH-018 product by reason that it is crystallized and taken a form, which it was poured.
13. Crystallized JWH-018 product is taken out and crushed. Then, It is air dried on a paper or a dish in a warm dry well ventilated room (better to use vacuum desiccator to significantly increase drying speed). Drying procedure depends on amount of JWH-018 product and takes ~48 h. Reaction yield is 3000 g.
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