Made My Compound🎉
Sunday, October 12
157.6 lbs (from 165.4 lbs on Aug 24) | 🏃🏻 Done (6/6)
Not really related to the main topic, but I posted a panel from the Naver webtoon Parenting Diary (육아일기) because it’s just too cute. 😊
I got through a good yoga class and headed back to the lab to rerun the reaction I planned yesterday. I double-confirmed that the HATU-mediated coupling is painfully sluggish, so I decided to generate the acid chloride first. I found a literature example with a closely related substrate and set up that route as well. One more key observation: even with the acid chloride formed cleanly, the reaction barely moved after adding the nucleophile. I quenched and tried to purify both runs, but the starting material co-eluted on reversed phase, so separation was tough. I’ll reset the conditions and keep pursuing the acid-chloride approach.
It’s draining to wrestle with this for a week without a clean win, but each attempt suggests the next step. I don’t feel stuck. There are still several things to try, so I’m hopeful👍
Monday, October 13
157.1 lbs (from 165.4 lbs on Aug 24) | 🏃🏻 Done (1/6)
Fresh Monday workout, then back to the synthesis. I suspected the slow reaction after adding the nucleophile was due to its low solubility in the solvent, so I evaporated DCM right after confirming acid-chloride formation and then added a base + nucleophile + DMF mixture. But about 60% of the acid chloride hydrolyzed back to the acid; DMF was clearly too wet. I quickly reset the reaction, added the amine as a solid with twice the equivalents, and minimized air exposure, but it still crawled🧐
I dug into the literature for this nucleophile and finally found a close precedent: they used 10(!) equivalents of amine with base(15eq.) in acetonitrile, and stirred at 70°C. Holy moly. I charged the mixture with the extra equivalents, grabbed dinner, and came back to check. There was still a lot of starting material, but I tried purification anyway. Two runs later, I left after 10 p.m. Starting the week like this is a bit draining, but YSD is moving fast, so I really need to get this compound made this week.
Between chemistry experiments, I met with Kevan to catch up. I drafted a short thesis-project summary to send to potential qualifying-exam committee members; he gave great feedback on tightening it up! Once Bill confirms, I’ll send it out.
Tuesday, October 14
155.9 lbs (from 165.4 lbs on Aug 24) | 🏃🏻 Done (2/6)
Today I skipped chemistry and focused on biology experiments. I caught an interesting journal club talk in the middle of the day and, for the first time in a while, left work at a reasonable hour. I took a run on a different route, which was really beautiful🥹 Also, running definitely lifted my mood.
When I’m learning from someone, I have to build my schedule around the person training me, which makes it hard to eat or rest when I want. It’s a bit more tiring and stress management isn’t easy, but that’s how beginnings are! I just hope to adapt quickly.
Wednesday, October 15
155.3 lbs (from 165.4 lbs on Aug 24) | 🏃🏻 Done (3/6)
Today was another busy day. In the morning I kept building the YSD library, then headed to the DeGrado lab group meeting. I gave a short journal review, which ran longer than I expected, but it was a good opportunity. I worked at the bench until ~3 pm with no time for lunch and then attended the Shokat lab group meeting. Daunting day😵 Right after, I checked the NMR of the purified product from the last attempt, but it was still impure. Not a great feeling, but I have one more refinement to try, so I wrapped up quickly and went home. After deep-cleaning the house and doing laundry, including the duvet, cover, and pillowcases, I cleared my head and felt much better. Hopefully tomorrow will be my final attempt to make this compound.
Thursday, October 16
155.5 lbs (from 165.4 lbs on Aug 24) | 🏃🏻 Done (4/6)
After a workout I went straight to the dentist for a six-month checkup. The dentist had changed, and suddenly I was told I needed treatment😕 My previous dentist had said we could just monitor it, but the new doctor strongly recommended a filling and even suggested a product called “Limelite” that would have cost $150 after insurance. I pushed back, since it didn’t seem necessary for a mild case, and we agreed on a simple filling. Thanks to insurance, it cost only a few dozen dollars. Still, my former dentist felt more thorough and kind; I may look for a clinic closer to home.
In the afternoon I tackled the stubborn synthesis again, paying attention to every detail I could think of. The yield wasn’t what I had hoped, but by 10pm, I finally felt confident I had a clean compound. I’ll confirm tomorrow! During my master’s, without LC–MS, I relied entirely on TLC and NMR; working in a well-equipped lab here, I have gotten somewhat lazy about the basics. Returning to fundamentals solved the problem surprisingly quickly. Stay grounded in the basics while making full use of the tools I have🫡
Friday, October 17
154.7 lbs (from 165.4 lbs on Aug 24) | 🏃🏻 Done (5/6)
Today I finally obtained the compound I needed🎉🎉 It was a good reminder to recheck the basic principles of organic chemistry that I learned during my master’s. After joining the lab I assumed I wouldn’t use those skills again, since my prospective thesis topic was far from synthesis. But I ended up needing them, and I will be using them again on a side project with a DeGrado lab postdoc, where I will synthesize substrates to test a de novo enzyme he designed. It feels great to still have those skills; I try to keep them sharp!
In the afternoon I spent the whole time on biology. Now that I have the compound, I’m no longer the bottleneck, so I feel much more relaxed even though the it was busy. After work I went for my first run in a few days. Maybe because I added tib raises to my routine this week, the run felt easier, probably a exercise worth keeping.
Saturday, October 18
153.4 lbs (from 165.4 lbs on Aug 24) | 🏃🏻 Done (6/6)
I got a haircut today (one month after the last one). I don’t know why, but I was so sleepy that I literally fell into REM sleep during the cut. Maybe that’s why my hair looks a little different from last time😳. Still, the designers (a husband-and-wife team💪) are always very kind and professional. Funny thing: I’m in a cutting phase, and they noticed I’d lost weight just by looking at my face. Since I see my face and body every day, it’s hard to notice progress, but someone who only sees me once a month can spot the difference much more easily. I was happy that it indirectly proved the process is going well. I’ll probably cut for another month; my body fat is around 13.5% now, and I feel better than ever. I’m looking forward to the bulking phase after this!
After the haircut, I had lunch at a Chinese restaurant I went to last time with a friend. The designer recommended it, and I had wontons. They were so good that I wanted to try other dishes too. The beef chow mein was delicious, though I think Capital does it better to be honest. Full and happy, I wrote a bit of my blog and then slept well.
