US 11,891,412 B2
Production of highly fat-soluble phosphoramidite
Tsuyoshi Fujihara, Kobe (JP); Kenichi Nakamura, Kobe (JP); Toru Kurome, Kobe (JP); Daisuke Sasahara, Kobe (JP); Akiko Shimahara, Kobe (JP); and Masahiro Neya, Kobe (JP)
Assigned to KNC LABORATORIES CO., LTD., Hyogo (JP)
Appl. No. 16/958,100
Filed by KNC LABORATORIES CO., LTD., Kobe (JP)
PCT Filed Dec. 26, 2018, PCT No. PCT/JP2018/047748
§ 371(c)(1), (2) Date Sep. 17, 2020,
PCT Pub. No. WO2019/131719, PCT Pub. Date Jul. 4, 2019.
Claims priority of application No. 2017-252107 (JP), filed on Dec. 27, 2017.
Prior Publication US 2021/0087220 A1, Mar. 25, 2021
Int. Cl. C07H 21/04 (2006.01)
CPC C07H 21/04 (2013.01) 6 Claims
 
1. A method for preparing a compound represented by formula (I):

OG Complex Work Unit Chemistry
[wherein,
R1 represents an optionally substituted C6-C30 alkyloxy group, and the substituent is at least one group selected from a C1-C3 alkyl group or a C3-C6 cycloalkyl group,
R2 each independently represents an optionally substituted C1-C6 alkyl group, and the substituent is at least one group selected from a C1-C3 alkyl group or a C3-C6 cycloalkyl group, and
R3 represents an optionally substituted C6-C30 alkyloxy group, an optionally substituted C1-C8 alkyloxy group, or an optionally substituted C2-C8 alkynyloxy group, and the substituent in the optionally substituted C6-C30 alkyloxy group is at least one group selected from a C1-C3 alkyl group, or a C3-C6 cycloalkyl group, and the substituent in the optionally substituted C1-C8 alkyloxy group or the optionally substituted C2-C8 alkynyloxy group is a cyano group (CN)],
which comprises the following steps:
(1) reacting an aliphatic alcohol and a trivalent phosphorus compound in organic solvent in the presence of an activator or an organic base;
(2) washing the resulting reaction mixture with water in a separatory funnel;
(3) recovering the organic layer after the step (2) and concentrating it (with the proviso that when the organic solvent used in the step (1) is a nitrile solvent, the steps (2) to (3) may be omitted);
(4) solubilizing the resulting residue obtained in the step (3) in an aliphatic hydrocarbon solvent (with the proviso that when the organic solvent used in the step (1) is an aliphatic hydrocarbon solvent, the steps (2) to (3) may be omitted);
(5) washing the aliphatic hydrocarbon solution prepared in the step (4) with a nitrile solvent in a separatory funnel;
(6) recovering the aliphatic hydrocarbon solution after the step (5) to obtain a solution of a phosphoramidite compound.