Acetic Acid → tert-butyl 4-(4-((S)-1-(4-((S)-4-isopropyl-2-oxooxazolidin-3-yl)pyrimidin-2-ylamino)ethyl)benzyl)-2,2-dimethylpiperazine-1-carboxylate

HRID 1850127Notes

Reaction equation

HRID 1850127 reaction equation
[CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C@H:17]([C:19]2[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=2)[CH3:18])[N:11]=1)([CH3:3])[CH3:2].[CH3:27][C:28]1([CH3:41])[CH2:33][NH:32][CH2:31][CH2:30][N:29]1[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].C(O)(=O)C>CO.O.CCOC(C)=O>[CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C@H:17]([C:19]2[CH:26]=[CH:25][C:22]([CH2:23][N:32]3[CH2:31][CH2:30][N:29]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:28]([CH3:41])([CH3:27])[CH2:33]3)=[CH:21][CH:20]=2)[CH3:18])[N:11]=1)([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 299224001,1-Dimethylethyl 2,2-dimethyl-1-piperazinecarboxylateHCID 867301594-((S)-1-(4-((S)-4-isopropyl-2-oxooxazolidin-3-yl)pyrimidin-2-ylamino)ethyl)benzaldehyde

Product 1

HCID 86730161tert-butyl 4-(4-((S)-1-(4-((S)-4-isopropyl-2-oxooxazolidin-3-yl)pyrimidin-2-ylamino)ethyl)benzyl)-2,2-dimethylpiperazine-1-carboxylateYield 72.4%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 4-((S)-1-(4-((S)-4-isopropyl-2-oxooxazolidin-3-yl)pyrimidin-2-ylamino)ethyl)benzaldehyde (71 mg, 0.2 mmol) and tert-butyl 2,2-dimethylpiperazine-1-carboxylate (47.1 mg, 0.22 mmol) in MeOH (4 mL) was added acetic acid (14.4 mg, 0.24 mmol) and 5-Ethyl-2-methylpyridine borane complex (27 mg, 0.2 mmol, sigma aldrich). The solution was stirred at 50° C. for 4 h then 5 drops of water was added. The solution was stirred at room temperature for another 2 h then diluted with EtOAc (10 mL) and washed with water (10 mL). After separation, the aqueous phase was extracted with EtOAc (3×10 mL). Combined organics were dried over Na2SO4, filtered and concentrated. The crude material was purified through Silica gel column chromatography (MeOH/EtOAc 0 to 10%) to give tert-butyl 4-(4-((S)-1-(4-((S)-4-isopropyl-2-oxooxazolidin-3-yl)pyrimidin-2-ylamino)ethyl)benzyl)-2,2-dimethylpiperazine-1-carboxylate as a white solid (80 mg, 72.4% yield).

Workup

  1. stirringThe solution was stirred at room temperature for another 2 h
  2. washwashed with water (10 mL)
  3. customAfter separation
  4. extractionthe aqueous phase was extracted with EtOAc (3×10 mL)
  5. dry with materialCombined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified through Silica gel column chromatography (MeOH/EtOAc 0 to 10%)

Sources & evidence

ORD record
ord-b286a133347748c7ac972e2363615d96
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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