Method for producing polyalkylene glycol derivative having amino group at end, polymerization initiator for use in the same, and alcohol compound as raw material for the polymerization initiator

Patent metadata

Field	Value
Publication number	US-9708350-B2
Application number	US-201514959318-A
Country	US
Kind code	B2
Filing date	Dec 4, 2015
Priority date	Dec 4, 2014
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

A method for producing a narrowly distributed and high-purity polyalkylene glycol derivative having an amino group at an end, a polymerization initiator for use in the method, and a precursor of the polymerization initiator are provided.
The present invention provides: a method for producing a polyalkylene glycol derivative having an amino group at an end, using, as a polymerization initiator, a compound represented by the general formula (I); a compound represented by the following general formula (I); and a precursor thereof:

wherein R A 1a and R A 1b each independently represent a protective group of the amino group, or one of R A 1a and R A 1b represents H and the other represents a protective group of the amino group, or R A 1a and R A 1b bind to each other to represent a cyclic protective group forming a ring; R A 2 represents a linear, branched, or cyclic hydrocarbon group having 1 to 6 carbon atoms; R A 3 represents a single bond, or a linear, branched, or cyclic hydrocarbon group having 1 to 20 carbon atoms, and the hydrocarbon group may contain a heteroatom; the total number of carbon atoms (or the total number of carbon atoms and heteroatoms) of R A 2 and R A 3 is 4 or more; and M represents an alkali metal.

First claim

What is claimed is:

1. A method for producing a polyalkylene glycol derivative having an amino group at an end, comprising at least a step of reacting a polymerization initiator represented by the following general formula (I) with an alkylene oxide:

wherein R A 1a and R A 1b each independently represent a protective group of the amino group, or one of R A 1a and R A 1b represents a hydrogen atom and the other represents a protective group of the amino group, or R A 1a and R A 1b bind to each other to represent a cyclic protective group forming a ring together with a nitrogen atom of the amino group, and wherein the protective group is selected from any one of the following (P-1) to (P-4):
(P-1), a protective group of a structure represented by Si(R 1 ) 3 (trialkylsilyl group), wherein each R 1 independently represents a linear monovalent hydrocarbon group having 1 to 6 carbon atoms, or a branched or cyclic monovalent hydrocarbon group having 3 to 6 carbon atoms, or independent R 1 s may be bonded to each other to form a 3 to 6 membered ring together with the silicon atom bonded to the independent R 1 s;
(P-2), a protective group of a structure represented by R A 6 OCO, wherein R A 6 represents a residue of a monovalent hydrocarbon having 1 to 20 carbon atoms, and the residue may contain a halogen atom, an oxygen atom, a nitrogen atom, a sulfur atom, a silicon atom, a phosphorus atom, or a boron atom;
(P-3), a cyclic protective group formed by R A 1a and R A 1b wherein R A 1a and R A 1b bind to each other, selected from an N-phthaloyl group, an N-tetrachlorophthaloyl group, an N-4-nitrophthaloyl group, an N-dithiasucciloyl group, an N-2,3-diphenylmaleoyl group, an N-2,5-dimethylpyrrolyl group, an N-2,5-bis(triisopropylsiloxy)pyrrolyl group, an N-1,1,3,3-tetramethyl-1,3-disilaisoindolyl group, a 3,5-dinitro-4-pyridonyl group, and a 2,2,5,5-tetramethyl-2,5-disila-1-azacyclopentane; and
(P-4), a protective group selected from a benzyl group, a p-methoxybenzyl group, a p-toluenesulfonyl group, a 2-nitrobenzenesulfonyl group, a (2-trimethylsilyl)ethanesulfonyl group, an allyl group, a pivaloyl group, a methoxymethyl group, a di(4-methoxyphenyl)methyl group, a 5-dibenzosuberyl group, a trinylmethyl group, a (4-methoxyphenyl)diphenylmethyl group, a 9-phenylfluorenyl group, a [2-(trimethylsilyl)ethoxy]methyl group, and an N-3-acetoxypropyl group;
R A 2 represents a linear divalent hydrocarbon group having 1 to 6 carbon atoms, or a branched or cyclic divalent hydrocarbon group having 3 to 6 carbon atoms;
R A 3 represents a single bond, or a linear divalent hydrocarbon group having 1 to 20 carbon atoms, or a branched or cyclic divalent hydrocarbon group having 3 to 20 carbon atoms, and the hydrocarbon group may comprise a heteroatom;
a total number of carbon atoms of R A 2 and R A 3 is 4 or more, or in a case in which R A 3 comprises a heteroatom, a total number of carbon atoms and heteroatoms of R A 2 and R A 3 is 4 or more; and
M represents an alkali metal.

2. A method for producing a polyalkylene glycol derivative having an amino group at an end, comprising the following Step a) to Step c):

wherein R A 1a and R A 1b each independently represent a protective group of the amino group, or one of R A 1a and R A 1b represents a hydrogen atom and the other represents a protective group of the amino group, or R A 1a and R A 1b bind to each other to represent a cyclic protective group forming a ring together with a nitrogen atom of the amino group, and wherein the protective group is selected from any one of the following (P-1) to (P-4):
(P-1), a protective group of a structure represented by Si(R 1 ) 3 (trialkylsilyl group), wherein each R 1 independently represents a linear monovalent hydrocarbon group having 1 to 6 carbon atoms, or a branched or cyclic monovalent hydrocarbon group having 3 to 6 carbon atoms, or independent R 1 s may be bonded to each other to form a 3 to 6 membered ring together with the silicon atom bonded to the independent R 1 s;
(P-2), a protective group of a structure represented by R A 6 OCO, wherein R A 6 represents a residue of a monovalent hydrocarbon having 1 to 20 carbon atoms, and the residue may contain a halogen atom, an oxygen atom, a nitrogen atom, a sulfur atom, a silicon atom, a phosphorus atom, or a boron atom;
(P-3), a cyclic protective group formed by R A 1a and R A 1b wherein R A 1a and R A 1b bind to each other, selected from an N-phthaloyl group, an N-tetrachlorophthaloyl group, an N-4-nitrophthaloyl group, an N-dithiasucciloyl group, an N-2,3-diphenylmaleoyl group, an N-2,5-dimethylpyrrolyl group, an N-2,5-bis(triisopropylsiloxy)pyrrolyl group, an N-1,1,3,3-tetramethyl-1,3-disilaisoindolyl group, a 3,5-dinitro-4-pyridonyl group, and a 2,2,5,5-tetramethyl-2,5-disila-1-azacyclopentane; and
(P-4), a protective group selected from a benzyl group, a p-methoxybenzyl group, a p-toluenesulfonyl group, a 2-nitrobenzenesulfonyl group, a (2-trimethylsilyl)ethanesulfonyl group, an allyl group, a pivaloyl group, a methoxymethyl group, a di(4-methoxyphenyl)methyl group, a 5-dibenzosuberyl group, a trinylmethyl group, a (4-methoxyphenyl)diphenylmethyl group, a 9-phenylfluorenyl group, a [2-(trimethylsilyl)ethoxy]methyl group, and an N-3-acetoxypropyl group;
R A 2 represents a linear divalent hydrocarbon group having 1 to 6 carbon atoms, or a branched or cyclic divalent hydrocarbon group having 3 to 6 carbon atoms;
R A 3 represents a single bond, or a linear divalent hydrocarbon group having 1 to 20 carbon atoms, or a branched or cyclic divalent hydrocarbon group having 3 to 20 carbon atoms, and the hydrocarbon group may comprise a heteroatom;
a total number of carbon atoms of R A 2 and R A 3 is 4 or more, or in a case in which R A 3 comprises a heteroatom, a total number of carbon atoms and heteroatoms of R A 2 and R A 3 is 4 or more;
R A 4 represents a hydrogen atom, or a linear, branched, or cyclic hydrocarbon group that may be substituted, the hydrocarbon group having 1 to 12 carbon atoms, and the hydrocarbon group may comprise a heteroatom;
R A 5 represents an alkylene group having 2 to 8 carbon atoms;
M represents an alkali metal; and
n represents an integer of 1 to 450;
Step a)
reacting a polymerization initiator represented by the general formula (I) with an alkylene oxide in a polymerization solvent to obtain a compound represented by the following general formula (I-1):

wherein R A 1a , R A 1b , R A 2 , R A 3 and R A 5 are the same as defined in the general formula (II);
M represents an alkali metal and is the same as M in the general formula (I); and
r represents an integer of 1 to 445;
Step b)
reacting the compound represented by the general formula (I-1) with a compound represented by the following general formula (I-2) to obtain a compound represented by the general formula (II):
R A 4 (OR A 5 ) k L  (I-2)

wherein R A 4 and R A 5 are the same as defined in the general formulas (II) and (III);
k represents an integer of 0 to 5; and
L represents a leaving group; and
Step c)
deprotecting the compound represented by the general formula (II) to obtain a compound represented by the general formula (III).

Assignees

• Shinetsu Chemical Co

Inventors

• Suka Yuki
• Harada Yuji
• Watanabe Takeru
• Nonaka Shiori

Classifications

• C08G65/2639

  the other compounds containing elements other than oxygen, nitrogen or sulfur · CPC title

• C08G65/2609

  containing aliphatic hydroxyl groups · CPC title

• C08G65/2618

  the other compounds containing nitrogen · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C08G65/329

  with organic compounds · CPC title