Method for producing nucleic acid oligomer

A method for producing a nucleic acid oligomer represented by the following formula (2′), the method comprising:

• reacting a nucleic acid oligomer represented by the formula (1) with a dichloroacetic acid solution having a molar ratio of formaldehyde to dichloroacetic acid, formaldehyde mol/dichloroacetic acid mol, of 90×10−6 or less:
• wherein
• G2 represents a protecting group of a hydroxyl group,
• Ba is the same or different and each independently represents a nucleobase which optionally protected with a protecting group,
• R1, R2 and R3 are the same or different and each independently represent a hydrogen atom or an alkoxy group,
• R is the same or different and each independently represents a protected hydroxyl group, a hydrogen atom, a fluorine atom, a methoxy group, a 2-methoxyethyl group, or an OQ′ group,
• Q′ is the same or different and each independently represents a methylene group bonded to a carbon atom at a 4′-position of ribose, an ethylene group bonded to a carbon atom at a 4′-position of ribose, or an ethylidene group bonded to a carbon atom at a 4′-position of ribose,
• Y is the same or different and each independently represents an oxygen atom or a sulfur atom,
• n represents an integer of from 1 to 200,
• W1 represents an OZ group and X1 represents an R group, or
• W1 represents an OV group, and X1 represents an OZ group,
• V represents a protecting group of a hydroxyl group,
• Z is a group having a structure including a solid support and a linking group, and
• when n is an integer of 2 or more, a non-nucleotide linker is optionally incorporated between respective nucleotides in the nucleic acid oligomer represented by the formula (1);
• and
• wherein
• G2, Ba, R, Y, X1, W1, and n are as in the formula (1), and
• a non-nucleotide linker is optionally incorporated between respective nucleotides in the nucleic acid oligomer represented by the formula (2);
• removing a group represented by Z from the nucleic acid oligomer represented by the formula (2);
• and
• removing a protecting group of a hydroxyl group and a nucleobase:
• wherein
• Y and n are as in the formula (1),
• Be is the same or different and each independently represents a nucleobase,
• G4 is the same or different and each independently represents a hydrogen atom, an alkali metal ion, an ammonium ion, an alkylammonium ion, or a hydroxyalkylammonium ion,
• R′ is the same or different and each independently represents a hydroxyl group, a hydrogen atom, a fluorine atom, a methoxy group, a 2-methoxyethyl group, or an OQ′ group,
• Q′ is as in the formula (1),
• X3 and W3 each independently represent a hydroxyl group, or
• X3 represents an R′ group, and W3 represents a hydroxyl group.

A dichloroacetic acid solution, comprising:

• formaldehyde;
• and
• dichloroacetic acid,
• wherein a molar ratio of formaldehyde to dichloroacetic acid, formaldehyde mol/dichloroacetic acid mol, is 90×10−6 or less.