---
title: "From Synthesis to Final Product: Yield, Deprotection, and Purification Explained"
description: "From Synthesis to Final Product: Yield, Deprotection, and Purification Explained"
image: https://blog.sierrabio.com/hubfs/business%20graph%20of%20success%20in%20blues%20and%20black%20colours%20with%20nice%20light%20effects.jpeg
---

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# From Synthesis to Final Product: Yield, Deprotection, and Purification Explained

![Harold Devoz](https://app.hubspot.com/settings/avatar/d41d8cd98f00b204e9800998ecf8427e)

 Harold Devoz

March 3, 2026

### Why Yield Drops Faster Than You Expect

Even with **99% coupling efficiency**, yields compound quickly. A 100-base oligo may produce less than 40% crude yield — before purification.

### Improving Coupling Efficiency

- Eliminate moisture
- Optimize reagent volumes and timing
- Choose appropriate solid supports
- Maintain fresh reagents

### Cleavage and Deprotection

Cleavage releases the oligo from the solid support, while deprotection removes chemical protecting groups. Conditions vary based on oligo type and modifications.

RNA oligos require an additional **2′-deprotection step**, making protocol selection especially important.

### Purification Options

Common methods include:

- Desalting (low purity)
- Cartridge purification
- Reverse-phase HPLC
- Anion-exchange HPLC
- PAGE for long or highly structured oligos

The right method depends on oligo length, application, and purity requirements.

### Final Thought

Understanding yield, purification, and analytical methods ensures you select the correct synthesis scale and avoid costly rework.

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## Keep reading

### [![](https://blog.sierrabio.com/hs-fs/hubfs/Chemist%20holding%20up%20beaker%20of%20green%20chemical%20in%20the%20laboratory.jpeg?width=1000&height=667&name=Chemist%20holding%20up%20beaker%20of%20green%20chemical%20in%20the%20laboratory.jpeg) Lab Setup, Safety, and Compliance for In-House Oligo Synthesis](https://blog.sierrabio.com/lab-setup-safety-and-compliance-for-in-house-oligo-synthesis)

### [![](https://blog.sierrabio.com/hs-fs/hubfs/Large-Scale-Apparatus.jpg?width=900&height=696&name=Large-Scale-Apparatus.jpg) Choosing the Right Oligonucleotide Synthesizer for Your Lab](https://blog.sierrabio.com/choosing-the-right-oligonucleotide-synthesizer-for-your-lab)

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