Sodium methanolate methanol → 7-((S)-5-hydroxymethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

HRID 1162896Notes

Reaction equation

HRID 1162896 reaction equation
[OH:1][C@H:2]([CH2:26][OH:27])[CH2:3][NH:4][C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])[NH:11][C:12]2=[O:15])=[CH:7][CH:6]=1.[CH3:28][O-:29].[Na+].CO>C(=O)(OCC)OCC>[OH:27][CH2:26][C@H:2]1[O:1][C:28](=[O:29])[N:4]([C:5]2[CH:14]=[C:13]3[C:8]([CH:9]=[C:10]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[C:22]([F:25])([F:23])[F:24])[NH:11][C:12]3=[O:15])=[CH:7][CH:6]=2)[CH2:3]1

Participants

4

Reactant 2

HCID 23694274Sodium methanolate methanolHCID 59520049HCID 59520049, compound

Product 1

HCID 118536727-((S)-5-hydroxymethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-oneYield 78%

Reagents, catalysts & solvents 1

HCID 7766Diethyl CarbonateSolvent

Conditions

Temperature
105 °C

Procedure

The 7-((S)-2,3-dihydroxypropylamino)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (281.9 mg, 0.745 mmol) obtained in step A was suspended in diethyl carbonate (2.93 ml), and thereafter, a 28% sodium methoxide-methanol solution (117 μl) was added thereto. The obtained mixture was stirred at 105° C. for 13 hours. Thereafter, diethyl carbonate was distilled away under reduced pressure. The obtained residue was dissolved in methanol (15 ml), and the obtained solution was stirred under heating to reflux for 10 minutes. Thereafter, the reaction solution was concentrated, and a saturated ammonium chloride aqueous solution was then added to the residue, followed by extraction with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and was then concentrated. The obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=40:1 to 20:1), so as to obtain 7-((S)-5-hydroxymethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (233.8 mg; yield: 78%).

Workup

  1. distillationThereafter, diethyl carbonate was distilled away under reduced pressure
  2. dissolutionThe obtained residue was dissolved in methanol (15 ml)
  3. stirringthe obtained solution was stirred
  4. temperatureunder heating
  5. temperatureto reflux for 10 minutes
  6. concentrationThereafter, the reaction solution was concentrated
  7. additiona saturated ammonium chloride aqueous solution was then added to the residue
  8. extractionfollowed by extraction with ethyl acetate
  9. dry with materialThe extract was dried over anhydrous sodium sulfate
  10. concentrationwas then concentrated
  11. customThe obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=40:1 to 20:1)

Sources & evidence

ORD record
ord-73d7a848f2324c1a92ca8bdc588acf8b
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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