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1.3 Which Scale? (PDF version)

Most reactions tried for the first time will most likely not work at all or work badly therefore it is essential to limit the scale of the reaction the first time it is tried.
Use the following scale as a guide: in general 50 mg - this ammount should be adjusted up or down based on:

  1. The availability of the starting material.

If the starting material is cheap/requires just a few steps to make and you have lots available

  1. How easy it is to carry the reaction on a very small scale e.g:

(a) anhydrous reaction  with exactly 1 eq of LDA would be very difficult.
(b) addition of a catalyst requiring less than 1 mg,
(c) solvent free reactions – not enough material to stir together

Scale up: Factor of 5

When scaling up a reaction do so in orders of 5 magnitudes maximum.
Therefore carry out the reaction 3-4 times in increasing scales before carrying out on >10g scale. Losing this quantity of material in a synthesis could be catostrophic!!!!!
Exceptions: when starting material is very cheap and you are following a known procedure and the product needs to be distilled.

Make sure you are happy with the yield before moving to the next scale up – don´t just hope it will get better.
Note! On very small scale the yield might not be reliable (up or down). For example the presence of small impurities/solvents/variations in the balance might make it seems that the yield is higher than really is – therefore dissapointment when scaling up to 250mg-0.5g.


Next - 1.4 Screening Conditions