It happened in February or March of 1994. At that time my office was located in the room just in front of the library in Building 1; I do not remember exactly what I was doing when the phone in my office rang. However, I remember perfectly the rest.
Dionisio, can you come to my office, please? It was the voice of the Engineer Ivan Villax on the phone.
DM: Yes, I'll be over.
IV: Thanks
When I arrived at IV's office and after greeting me he invited me to sit down in front of him.
IV: Would you like a coffee? He used to offer me a coffee.
IV: Look, I have a problem. A big pharmaceutical company asked Hovione to prepare a few kilos of a compound to be used in clinical trials of a new drug candidate. It happens that the process is very dangerous and people here do not think we should do it. I pledged my word of honour as chemist with this company to do it. Dionisio, I want you to take these papers and study the process. You can go home for one or two days if you prefer and come back once you have studied the process. Then come back again to my office and tell me if the process can be done or not. But look…
the Engineer Villax lifted up his forefinger
…if you say that the process cannot be done, nothing happens because here nobody wants to do it but if you say that it can be done, you will do it.
The technical information of the process consisted in a five steps recipe including the analytical conditions for the IPC, the reaction schemes and a diagram with the configuration of the reaction unit for steps 3 and 5 (the two steps using DIBAC). The second step of the process was a dehydrobromination using Sodium hydride, the fourth step was a reduction with Lithium Aluminium Hydride and third and fifth steps were using DIBAC.
For the people less familiar with these reagents, Sodium hydride and Lithium Aluminium Hydride are reagents that need to be handled with precaution (exclusion of moisture) as they react vigorously with water evolving hydrogen. Nevertheless they are quite conventional reagents which are routinely used everywhere.
On the contary, DIBAC (diisobutylaluminium chloride) is a very strong reductor which reacts vigorously with water and with the oxygen of the air provoking self-ignition and explosion. It obliges work to be done in a specially designed reaction unit under strict conditions of water and air exclusion along all operations up to the total destruction of the excess of the reagent. The reaction and addition temperatures need to be maintained as low as below -70ºC in step 3 and -35ºC In step 5, which was an additional difficulty for the design of the unit and the execution of the process.
The next day I went back to the office of the Engineer Villax and I told him that the process was really dangerous but that my opinion is that everything can be done with the appropriate precautions and conditions and that the final was his as to whether the project was worth doing and the risk it involved.
Ivan Villax asked for me to explain how I planned to run the process. We both spent a couple of hours with me explaining and Ivan Villax putting questions, on how and where to run all the operations at both, lab scale and pilot scale. When at the end of the technical discussion Engineer Villax asked me what I would need to execute the project I said that we mainly needed two things
(a) to adapt a reactor in a small area and build up the special reaction unit for the DIBAC reactions and
(b) to select people with experience and rigor to run the pilot batches. We could not take more risks than those already known. Ivan Villax picked up the phone and asked Manuela Leite for Engineer Centeno to come tohis office.
Eng. Centeno was requested to give priority to all the necessary adaptation, work day and night, including week ends, everything that were necessary to speed up the project as by then we were already out of the committed delivery date of the product.
Josef Balin (a Hungarian chemist in training period with me at HQ) and myself run the lab preliminary trials in the Sala de Reagentes IV, which was a small isolated room just in the North-West top corner of Building 1.
(a) The group of the Eng. Centeno did an excellent wok and the special pilot unit in Building 9 and the rest of the adaptations in the area of Reagents in Building 1 were ready by April.
(b) José Carrilho and Alfredo André were assigned to take the responsibility of the pilot shifts.
The requested quantity of PP01 was 10 Kg and by 10th of June we were ready to deliver 12 kg of product meeting client tight specifications.
Some days later I was asked again to go to IV’s office. Eng. Villax expressed me his thanks and satisfaction for the results of the project. Some time later I heard that Eng. Villax had also requested the presence and personally expressed his thanks to José Carrilho and Alfredo André.
I always enjoyed working with Mr. Ivan Villax and will always remember his enthusiasm, resolution and clear code of principles.
|