@G.Patton
New Update:
Part I out of III, batch 003 (conversion to nordiazepam)
Procedure Used:
"To a vigorously stirred of 2-amino-5-chloro benzophenone (6.93 g, 1 mmol), chloroacetyl chloride (35.8 mL, 2 mmol) was added drop wise at room temperature under solvent-free conditions during 30 min and the progress of reaction was monitored by TLC. After completion of the reaction, NH4OAc (6.85 g, 3 mmol) and K2CO3 (12.5 g, 3 mmol) were added to the mixture at room temperature under solvent-free conditions and stirred for 2.5 h. When the reaction was completed, as it was shown by TLC, the water (300 mL) was added and the product was filtered off, washed with more water (2x 500 mL) and dried. The product was obtained in high yield and purity (94 % yield)"
Interesting enough, the more I scale up, the more yellowish the nordiazepam is.
Anyways, I used the rest of my chloroacetyl chloride (500mL is getting overnighted) up in order to produce the nor diazepam. Something strange happened...usually the solution is a pale yellow, but this time the solution was a red-orange color. The solution solidified! Perhaps all the chloroacetyl chloride was used up? Nonetheless, I proceeded with the wash. I ended up with a yellowish crystalline powder, which still has the right melting point. Im waiting on the Dragendorffs reagent spray to arrive, it will make the TLC analysis much easier. I ended up with 20 g of nordiazepam from the afromentioned batch (003) and a total of 15.3 g from Batch 01-003
Part II out of III, batch 002 (acetylation of nor diazepam)
Procedure Used for batch 002:
"To a vigorously stirred mixture of nordiazepam (1) (2.7 g, 1 mmol), a powder mixture of K2CO3 (5.5 g, 4 mmol)/KOH (2.2 g, 4 mmol) and acetic anhydride (excess 40 mL, 2 mmol) was added. The progress of the reaction was monitored by TLC. After completion of the reaction (3 h), water (3x100 mL) was added and the 1-acetyl-7-chloro-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (2) was easily isolated by a simple filtration, with 3x20omL water washes in more than 80 % yield with high purity. The product was used in the next step without any purification."
Batch 001 for Part II was 1/10 of the scale for batch 002, its a simple procedure. My lab tech forgot to put the filter paper on the fritted funnel and some product went through. We re ran the water back into the filter. I am not too happy with batch 001, I see foreign material in the compound and the yield was very low (40%).
Batch 002: I am letting this run overnight.
Conclusion: Once I collect 20 g of the acetylated nordiazepam, I will begin to convert this into alprozolam. Full report with video instructions coming soon
*The two photos added are the comparison between Part I, batch 002 and 003. Batch 002 was yellow and stayed in solution, while batch 003 was a dark orange color and solidified.
) into 1-acetyl-7-chloro-1H-benzo 1,4 diazepin. Then convert that into alprazolam, using hydrazine mono hydrate. I will be doing this step outside lol.
