Hydrochloric Acid → 2-[2-(2-{2-[2-(2-benzyloxyethoxy)ethoxy]ethoxy}ethoxy)ethoxy]ethyl carbonate (S)-2-oxo-3-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]-oxazolidin-5-ylmethyl ester

HRID 1162954Notes

Reaction equation

HRID 1162954 reaction equation
Cl[C:2](OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].[OH:14][CH2:15][C@H:16]1[O:20][C:19](=[O:21])[N:18]([C:22]2[CH:31]=[C:30]3[C:25]([CH:26]=[C:27]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[C:39]([F:42])([F:41])[F:40])[NH:28][C:29]3=[O:32])=[CH:24][CH:23]=2)[CH2:17]1.[CH2:43]([O:50][CH2:51][CH2:52][O:53][CH2:54][CH2:55][O:56][CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][OH:68])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.Cl>N1C=CC=CC=1>[O:21]=[C:19]1[N:18]([C:22]2[CH:31]=[C:30]3[C:25]([CH:26]=[C:27]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[C:39]([F:41])([F:40])[F:42])[NH:28][C:29]3=[O:32])=[CH:24][CH:23]=2)[CH2:17][C@@H:16]([CH2:15][O:14][C:2](=[O:3])[O:68][CH2:67][CH2:66][O:65][CH2:64][CH2:63][O:62][CH2:61][CH2:60][O:59][CH2:58][CH2:57][O:56][CH2:55][CH2:54][O:53][CH2:52][CH2:51][O:50][CH2:43][C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[O:20]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 821294-Nitrophenyl chloroformateHCID 11164646Hexaethylene Glycol Monobenzyl EtherHCID 118536727-((S)-5-hydroxymethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

Product 1

HCID 866267462-[2-(2-{2-[2-(2-benzyloxyethoxy)ethoxy]ethoxy}ethoxy)ethoxy]ethyl carbonate (S)-2-oxo-3-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]-oxazolidin-5-ylmethyl esterYield 37%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

4-Nitrophenyl chloroformate was added to 1 mL of a solution of 7-((S)-5-hydroxymethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one obtained in Step B of Example 1-13 (30 mg, 0.074 mmol) in pyridine, and the mixture was stirred at room temperature for six hours. Hexaethylene glycol monobenzyl ether (138 mg, 0.370 mmol) was added to the mixture which was then stirred at 60° C. for 14 hours. 1 N hydrochloric acid was added to the mixture, followed by extraction with ethyl acetate. The extract was washed with saturated saline and then dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (methylene chloride:methanol=50:1) to obtain 2-[2-(2-{2-[2-(2-benzyloxyethoxy)ethoxy]ethoxy}ethoxy)ethoxy]ethyl carbonate (S)-2-oxo-3-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]-oxazolidin-5-ylmethyl ester (22 mg, yield: 37%) as a colorless oil. The product was deprotected by a method similar to that of Example 1-36 using a 10% Pd—C catalyst in a hydrogen atmosphere to synthesize the title compound.

Workup

  1. stirringwas then stirred at 60° C. for 14 hours
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe extract was washed with saturated saline
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (methylene chloride:methanol=50:1)

Sources & evidence

ORD record
ord-5bf97790ce81495c9829a5360b08c724
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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