[Qfbale]

Have a nice day!
Hi, I am a master's student and i have almost no experience with chemical reactions. 
I have a compound that has a functional group of carboxylic acid, and this group must be changed to primary alcohol. My strategy have been:
Carboxilic acid pass to methyl ester
and methyl ester pass to Primary alcohol
But I have not had success with the reaction .
My system is buck under nitrogen atmosphere, use 3 equivalent of hydride, and the solvent is anhidrous ether, all at a reflux for 7 hours.
I've tried increasing the time, putting more hydride, but I can´t consume my whole substrate and the yield  is minimal.
Someone will experience about the best temperature and order of addition of reactants?
It would be better if I use tetrahydrofuran or anhydrous ether?
Thank you!

[TheUnassuming]

LAH should reduce and ester to an alcohol, the only question usually with LAH is whether it will also do other things that you don't want.  THF or ethyl ether are fine, basically any common ether solvent will work for LAH reductions as long as its dry.

A few questions/things to confirm:
Are you using 3 equivalents of LAH or hydride?
How pure is your starting material and how did you confirm this (NMR?)
What are you seeing by TLC when you run the reaction?   

[Qfbale]

Oh sorry, the reaction with my compound had not success. So, I tried to reduce a "control molecule" Betulinic acid to betulina. The reaction was done, but the yield was 60%. I want to improve the yield to optimize the conditions with the "control" to start to reduce my original compound.

But I dont know if my conditions are great. In my country, the humidity and hot is high, and I must be very minocious to control all conditions. There are some articles that shows O°C, ice bath, and others RT. Add LiAlH4 during the reaction in 3 ocassions has been documented. Others has been written that mantaining the reaction during 24 hours...
In your experience, what temperature do you use?
And other point, the nitrogen is very expensive and I'm using an open system that monitors if my system runs nitrogen. (a tube with glycerin).
If my reactions last long, the nitrogen tank ends very quickly.
I read that other people use balloons to maintain nitrogen and comes cheaper. You recommend?

[sjb]

One thing to note is that betulinic acid has a free hydroxyl, which may also be causing problems. How dry is the nitrogen?

[Qfbale]

It´s gas, is in the cylinder tank.

Thanks a lot.

[Dan]

I read that other people use balloons to maintain nitrogen and comes cheaper. You recommend?

Yes, definitely. A constant stream of nitrogen is probably not necessary.

If Acid Ester Alcohol is failing, there are some other options, including:

1. Acid alcohol with BH₃·THF or BH₃·SMe₂. BH₃ can also be generated in situ using 2NaBH₄ + I₂ 2BH₃ + 2NaI + H₂.
2. Acid mixed anhydride alcohol. The isobutyl anhydride is a common choice (made using isobuty chloroformate), and the anhydride can be reduced with NaBH₄.

[kriggy]

I had succes with NaBH₄-MeOH in THF:
ARKIVOC 2006 (i) 128-133
Simple reduction of ethyl, isopropyl and benzyl aromatic esters to
alcohols using sodium borohydride-methanol system Link.

Mod edit: Direct link added. Dan

[Dan]

I had succes with NaBH₄-MeOH in THF:
ARKIVOC 2006 (i) 128-133
Simple reduction of ethyl, isopropyl and benzyl aromatic esters to
alcohols using sodium borohydride-methanol system Link.

Mod edit: Direct link added. Dan

Reinventing the wheel somewhat - this was essentially done in the 80s using t-Butanol instead of THF, which they really should have cited:

Soai Synth. Commun. 1982, 12, 463 Link
Soai Bull. Chem. Soc. Jpn. 1984, 7, 1948 Link

^I used this procedure several years ago to reduce some polyhydroxylated lactones, kriggy's post reminded me, it works quite well.

[Qfbale]

I show you my compounds and my laboratory conditions .
First of all , I tried to reduce my compound that is a diterpene , but the reaction was not successful.
Then I tried to reduce a molecule that was already reduced before, my control is betulinic acid ( the reaction if conducted , but not all the reactant was consumed alcohol obtained with 60 % yield )
My interest molecule is the diterpene of the other image . I have very few milligrams of it, that is the reason that I want to improve the yield of my control.
from alcohol, then I want to change to aldehyde or pass to alcohol esthers .

Thank you so much.

[Dan]

Have you tried DIBAL?

[kriggy]

Lol at first I thought you are someone from my school because we have group working on betuline/betulinic acid :-D

There are more methods to reduce esters/produce alcohol/aldehyde:
1) sodium in dry alcohol at reflux like Org. Synth. 1934, 14, 20
DOI: 10.15227/orgsyn.014.0020

2) you might also try rosemund reduction: hydrogen + Pd, BaSO₄

3) or Hundsdicker reaction folowed by Delepine reaction: DOI: 10.15227/orgsyn.000.0000 (im not sure if you can distill the aldehyde)

4) or something like this: Org. Synth. 1946, 26, 97
DOI: 10.15227/orgsyn.026.0097

Just some random thoughts I found in my notes / books

[Qfbale]

Thank you. I have obtained my compounds!