Introduction
MDMB-INACA is important precursor for many synthetic cannabinoids like 5-CL-ADB-A (MDMB-4en-PINACA) (5Cl), 4F-MDMB-BINACA (4F), MDMB-BINACA and so one. It's widely sold by Chinese suppliers but it can be produced quite easily at home conditions. MDMB-INACA synthesis doesn't take elaborated or expensive equipment. Most part of necessary glassware and equipment may be substituted by DIY adaptations.
Difficulty rating: 2/10
Equipment and glassware:
- Flask 1 L;
- Magnetic stirrer;
- Funnel;
- Spatula;
- Laboratory scale (0.1 g-200 g is suitable);
- Measuring cylinders 100 ml and 20 ml;
- Beakers 5 L; 1 L; 500 ml x2; 100 ml x4;
- Drip funnel 250 ml;
- Laboratory grade thermometer (0 °C to 100 °C) ;
- Retort stand and clamp for securing apparatus;
- Buchner flask and funnel with vacuum pump (recommended but optional);
- Filter paper;
- DMF 500 ml;
- 1H-Indazole-3-carboxy acid (1) 35.3 g (0.215 mol) CAS 4498-67-3;
- tert-Leucine methyl ester hydrochloride (2) 56.7 g (0.312 mol) CAS 167223-43-0;
- Hydroxybenzotriazole hydrate (HOBT•H2O) 48 g CAS 123333-53-9;
- 1-Ethyl-3-carbodiimide (EDC•HCl) 82 g CAS 25952-53-8;
- Triethylamine 100 g;
- Brine solution ~2 L (NaCl);
- Distilled water;
MDMB-INACA (5Cl main precursor) Synthesis From 1H-indazole-3-carboxylic Acid Scheme
MDMB-INACA Synthesis From 1H-indazole-3-carboxylic Acid
1. DMF 500 ml is added to 1H-indazole-3-carboxy acid (1) 35.3 g (0.215 mol) in 1 L flask, the mixture is stirred.
2. Next, tert-Leucine methyl ester hydrochloride (2) 56.7 g (0.312 mol) is added and stirred until complete dissolution.
3. Then, hydroxybenzotriazole hydrate (HOBT•H2O) 48 g is poured into the mixture and stirred until complete dissolution.
4. Following step, 1-ethyl-3-carbodiimide (EDC•HCl) 82 g is added and stirred until complete dissolution.
5. Triethylamine 100 g is poured into the drip funnel and added dropwise with constant stirring (the mixture is turning cloudy). The reaction is exothermic and should be carried out slowly with constant stirring to avoid overheating. The higher temperature, the lower reaction yield.
6. The reaction mixture is stirred for one day (24 h).
7. The brine is added (at least 1 L), the mixture is diluted with more water volume in a larger vessel and stirred for ~20-30 min. Water is added until MDMB-INACA precipitate formation.
8. The MDMB-INACA precipitate is formed in the vessel’s bottom after stirring, it should be filtered.
MDMB-INACA yield is ~33 g (53%).
MDMB-INACA can be recrystallized from DMF or DMSO and precipitated with brine.
2. Next, tert-Leucine methyl ester hydrochloride (2) 56.7 g (0.312 mol) is added and stirred until complete dissolution.
3. Then, hydroxybenzotriazole hydrate (HOBT•H2O) 48 g is poured into the mixture and stirred until complete dissolution.
4. Following step, 1-ethyl-3-carbodiimide (EDC•HCl) 82 g is added and stirred until complete dissolution.
5. Triethylamine 100 g is poured into the drip funnel and added dropwise with constant stirring (the mixture is turning cloudy). The reaction is exothermic and should be carried out slowly with constant stirring to avoid overheating. The higher temperature, the lower reaction yield.
6. The reaction mixture is stirred for one day (24 h).
7. The brine is added (at least 1 L), the mixture is diluted with more water volume in a larger vessel and stirred for ~20-30 min. Water is added until MDMB-INACA precipitate formation.
8. The MDMB-INACA precipitate is formed in the vessel’s bottom after stirring, it should be filtered.
MDMB-INACA yield is ~33 g (53%).
MDMB-INACA can be recrystallized from DMF or DMSO and precipitated with brine.