Pyridine → 1-Chloroethyl 2,5,8,11,14-pentaoxahexadecan-16-yl carbonate

HRID 882369Notes

Reaction equation

HRID 882369 reaction equation
Cl[C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].[CH3:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][OH:24].N1C=CC=CC=1>C(Cl)Cl>[C:2](=[O:3])([O:24][CH2:23][CH2:22][O:21][CH2:20][CH2:19][O:18][CH2:17][CH2:16][O:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH3:8])[O:4][CH:5]([Cl:7])[CH3:6]

Participants

5

Reactant 3

HCID 1049PyridineHCID 90255Pentaethylene glycol monomethyl etherHCID 5213051-Chloroethyl chloroformate

Product 1

HCID 866963061-Chloroethyl 2,5,8,11,14-pentaoxahexadecan-16-yl carbonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Example 3, 1-chloroethyl chloroformate was reacted with pentaethylene glycol monomethyl ether (TCI) and pyridine in methylene chloride at −78° C. for 3 h to give 1-chloroethyl 2,5,8,11,14-pentaoxahexadecan-16-yl carbonate. This was then reacted with 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid in the presence of cesium carbonate in dimethylformamide overnight to give, after flash chromatography purification (hexane/ethyl acetate, 80/20 to 20/80), 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-[2-(2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-ethoxycarbonyloxy]-ethyl ester as a white solid. LCMS (ES+) m/z calcd. for C45H56Cl2F2N3O12 [(M+H)+]: 938, found: 938.

Sources & evidence

ORD record
ord-36a08773f9a74f6bb8405a5db485d5c0
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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