Method for producing hetero-type monodisperse polyethylene glycol derivative

A method for producing a hetero-type monodisperse polyethylene glycol represented by the formula (1), which comprises the following steps (A), (B), (C), (D), (E) and (F):

• wherein, in the formula (1), a represents an integer of 6 to 12,
• Step (A):
• a step of carrying out a nucleophilic substitution reaction between a compound of the formula (2) and a compound of the formula (3) so as to satisfy the requirement of the expression (F1) to obtain a compound of the formula (4):
• wherein, in the formula (2), b represents an integer of 3 to 9,
• wherein, in the formula (3), L represents a mesyl group or a tosyl group, R1 represents a trityl group or a benzyl group, and c represents an integer of 3 to 9,
• wherein, in the formula (4), R1 represents a trityl group or a benzyl group and a represents an integer of 6 to 12;
• Step (B):
• a step of carrying out Michael addition reaction of a compound of the formula (5) to the compound of the formula (4) obtained in the step (A) under a temperature condition of 10° C. or lower to obtain a compound of the formula (6),
• wherein, in the formula (5), R2 represents a hydrocarbon group having 1 to 6 carbon atoms,
• wherein, in the formula (6), R1 represents a trityl group or a benzyl group, R2 represents a hydrocarbon group having 1 to 6 carbon atoms, and a represents an integer of 6 to 12;
• Step (C):
• a step of detritylating or debenzylating the compound of the formula (6) obtained in the step (B) to obtain a reaction product containing a compound of the formula (7),
• wherein, in the formula (7), R2 represents a hydrocarbon group having 1 to 6 carbon atoms and a represents an integer of 6 to 12;
• Step (D):
• a step of purifying the compound of the formula (7) from the reaction product obtained in the step (C);
• Step (E):
• a step of reacting the compound of the formula (7) obtained in the step (D) with phthalimide and performing dephthalimidation to obtain a compound of the formula (8),
• wherein, in the formula (8), R2 represents a hydrocarbon group having 1 to 6 carbon atoms and a represents an integer of 6 to 12;
• and
• Step (F):
• a step of subjecting the compound of the formula (8) obtained in the step (E) to an acid hydrolysis treatment to obtain the compound represented by the formula (1).