/d/DrugManufacture

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I saw a paper years ago that broke down the synthesis of alprazolam. Can somebody help me find it?

by /u/Laedermaus · 0 votes · 2024-04-22 14:05:00

Years ago I was wondering how hard it would be to make xanax in a lab- At least pharma companies do it.
I found a very well detailed paper that explained it perfectly, and now I can't find it. Does anybody have that paper or any resources for manufacturing akprazolam?
.

Comments (4)
/u/BrohanSantana · N/A votes · 22nd April, 2024 - 14:45 · Link

If you find that will you send it to me, I was just looking for the same thing. Is there like a guidebook out there somewhere with the chemicals needed and molecule bonding you have to do because I want that

/u/Kyanite · N/A votes · 22nd April, 2024 - 14:59 · Link

bump for sauce

/u/mescalinedrink · N/A votes · 23rd April, 2024 - 00:26 · Link

WARNING: THIS SYNTHESIS IS HIGHLY COMPLEX, AND TAKES SEVERAL HOURS TO COMPLETE. IT ALSO INVOLVES HANDLING VOLATILE AND TOXIC CHEMICALS AND SHOULD ONLY BE ATTEMPTED BY A PROFESSIONAL. PROCEED WITH CAUTION. Raw Materials 2,6-Dichloro-4-phenylquinoline Hydrazine Hydrate Triethyl Orthoacetate Sodium Periodate Paraformaldehyde Phosphorus Tribromide Ammonia 6-Chloro-2-hydrazino-4-phenylquinoline: A stirred mixture of 2,6-dichloro-4-phenylquinoline (2.7 g, 0.01 mol) and hydrazine hydrate (6.8 g) was refluxed under nitrogen for 1 hour and concentrated in vacuo. The residue was suspended in warm water, and the solid was collected by filtration, dried and recrystallized from ethyl acetate-Skelly B hexanes to give 1.81g (67% yield) of 6-chloro-2-hydrazino-4-phenylquinoline of melting point 156.5°-157°C. 7-Chloro-1-methyl-6-phenyl-s-trizolo[4,3-a] quinoline: A stirred mixture of 6-chloro-2-hydrazino-4-phenylquinoline (1.4g,0.0052 mol),triethyl-orthoacetate (0.925g,0.0057 mol)and xylene (100 ml) was refluxed,under nitrogen, for2 hours 40minutes. During this period the ethanol formed in the reaction was removed by distillation through a short, glass helix-packed column. The mixture was concentrated to dryness in vacuo and the residue was crystallized from methanol ethyl acetate to give: 1.28 g of 7-chloro-1-methylB-phenyl-s-triazolo[4,3aI - quinoline (83.9% yield). The analytical sample was crystallized from methylene chloride:methanol and had a melting point 252.5C-253.5"C. 5-Chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone (Oxidation of 7-chloro-1-methyl-5-phenyl-s-trizolo[4,3-a] quinoline): A stirred suspension of 7-chloro-1-methyl-6-phenyl-s-triazolo[4,3-a] quinoline ( 2.94 g, 0.01 mol) in acetone (110 ml) was cooled in an ice-bath and treated slowly with a solution prepared by adding sodium periodate (2 g) to a stirred suspension of ruthenium dioxide (200 mg) in water (35 ml). The mixture became dark. Additional sodium periodate (8g) was added during the next 15 minutes. The ice bath was removed and the mixture was stirred for 45 minutes. Additional sodium periodate (4 g) was added and the mixture was stirred a t ambient temperature for 18 hours and filtered. The solid was washed with acetone and the combined filtrate was concentrated in vacuo. The residue was suspended in water and extracted with methylene chloride. The extract was dried over an- hydrous potassium carbonate and concentrated. The residue was chromatographed on silica gel (100 g) with 10% methanol and 90% ethyl acetate; 50 ml fractions were collected. The product was eluted in fractions 10-20 and was crystallized from ethyl acetate to give: 0.405 g of melting point 168O-169.5"C and 0.291 g of melting point 167.5'-169% (23.4% yield) of 5-chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone. The analytical sample had a melting point of 168C. 5-Chloro-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl] benzophenone: A stirred mixture of 5chloro-2-(3-methyl4H-1,2,4-triazolo4-yl)benzophenone, (2.98 g, 0.01 mol) para- formaldehyde (3 g) and xylene (100 ml) was warmed under nitrogen, in a bath maintained at 125°C for 7 hours. The mixture was then concentrated in vacuo. The residue was chromatographed on silica gel (150g) with 3% methanol 47% chloroform. Fifty ml fractions were collected. The product was eluted in fractions 20-44. The fractions were concentrated and the residue was crystallized from ethanol ethyl acetate to give: 1.64g of melting point 138°- 142°C; 0.316 g of melting point 138.5°-141°C; 0.431 g of melting point, 139°-141°C (72.8% yield) of 5-Chloro-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl] benzophenone. The analytical sample had a melting point of 138°-139°C. 5-Chloro-2-[3-(bromomethyl)-5-methyl-4H-1,2,4-triazol-4-yl] benzophenone.: A solution of 5chloro-2-[3-(hydroxymethyl)-5-methyl4H-l,2,4-triazol4-yl] -benzophenone (328 mg, 0.001 mol) in dry, hydrocarbon-stabilized chloroform (5 ml) was cooled in an ice-bath and treated with phosphorus tribromide (0.1 ml). The colorless solution was kept in the ice bath for 55 minutes, at ambient temperature (22°-24°C), for 5 hours. The resulting yellow solution was poured into a mixture of ice and dilute sodium bicarbonate. This mixture was extracted with chloroform. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated. The residue was crystallized from methylene chloride ethyl-acetate to give: 0.285 g of melting point 200°-240°C (decomposition) and 0.030 g of melting point 200°- 220°C (decomposition) of 5-Chloro-2-[3-(bromomethyl)-5-methyl-4H-1,2,4-triazol-4-yl] benzophenone. The analytical sample had a melting point of 200°-240°C. 8-Chloro-1-methyl-6-phenyl-4H-s-triazolo-[4,3a] [1,4]-benzodiazepine: A stirred suspension of 5-Chloro-2-[3-(bromomethyl)-5-methyl-4H-1,2,4-triazol-4-yl] benzophenone (391 mg, 0.001 mol) in tetrahydrofuran (15 ml) was cooled in an ice-bath and treated with a saturated solution of ammonia in methanol (12.5 ml). The resulting solution was allowed to warm to ambient temperature and stand for 24 hours. It was then concentrated in vacuo. The residue was suspended in water, treated with a little sodium bicarbonate and extracted with methylene chloride. The extract was washed with brine, dried with anhydrous potassium carbonate and concentrated. The residue was crystallized from methylene chloride ethyl acetate to give 0.220 g of crude product of melting point 227°-228.5°C. Recrystallization of this material from ethyl acetate gave 0.142 g of melting point 228°-229.5°C of 8-Chloro-1-methyl-6-phenyl-4H-s-triazolo-[4,3a] [1,4]-benzodiazepine.

/u/BrohanSantana · N/A votes · 23rd April, 2024 - 00:38 · Link

Yeah does sound difficult. Where do you find the raw substances to even do this?

/u/Laedermaus · N/A votes · 24th April, 2024 - 01:09 · Link

I love you so much

/u/Bromo54ur · N/A votes · 23rd April, 2024 - 02:08 · Link

Here's a couple. Not sure if these are what you had in mind, but there's several out there. You can use Scihub & search for the doi to get access tomost paywalled journal articles: https://sci-hub.3800808.com/10.1007/s00044-016-1585-z⚠️ https://www.tandfonline.com/doi/epdf/10.1080/25765299.2022.2117677?needAccess=true⚠️