Potassium Carbonate → HCID 68548704, compound

HRID 1446090Notes

Reaction equation

HRID 1446090 reaction equation
C([SiH2][O:6][C:7](C)(C)[CH:8]1[O:12][C:11](=[O:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17](B3OC(C)(C)C(C)(C)O3)=[C:16]([F:29])[CH:15]=2)[CH2:9]1)(C)(C)C.Br[C:33]1[CH:38]=[CH:37][C:36]([C:39]2([CH3:50])[O:43][C:42]3=[N:44][C:45]([N+:47]([O-:49])=[O:48])=[CH:46][N:41]3[CH2:40]2)=[CH:35][CH:34]=1.C([O-])([O-])=O.[K+].[K+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[F:29][C:16]1[CH:15]=[C:14]([N:10]2[CH2:9][CH:8]([CH2:7][OH:6])[O:12][C:11]2=[O:13])[CH:19]=[CH:18][C:17]=1[C:33]1[CH:38]=[CH:37][C:36]([C:39]2([CH3:50])[O:43][C:42]3=[N:44][C:45]([N+:47]([O-:49])=[O:48])=[CH:46][N:41]3[CH2:40]2)=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 68549369HCID 68549369, compoundHCID 131727902HCID 131727902, compound

Product 1

HCID 68548704HCID 68548704, compoundYield 16.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

3-[2-Fluoro-4′-(2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazol-2-yl)-biphenyl-4-yl]-5-hydroxymethyl-oxazolidin-2-one was synthesized according to the scheme shown in FIG. 7. To a dry round bottom flask was added 5-(tert-Butyl-dimethyl-silanyloxymethyl)-3-[3-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidin-2-one (148 mg, 0.33 mmol), 2-(4-Bromo-phenyl)-2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazole (˜97 mg, 0.3 mmol, impure), Ph(PPh3)4 (60 mg, 0.06 mmol) and K2CO3 (85 mg, 0.6 mmol). The flask was flushed with nitrogen and was added 4 mL degassed DMF/H2O (10/1, v/v). The resulting mixture was stirred at 80° C. for 2 hours before it was cooled down and partitioned in 60 mL EtOAc/60 mL water. The organic layer was washed with brine and dried over Na2SO4. Column chromatography (CH2Cl2/MeOH, v/v, 20:1 to 10:1) gave impure TBS-protected titled compound (˜22 mg) as yellow solid. This intermediate was dissolved in 2 mL THF and cooled to 0° C. TBAF (0.15 mL, 1M in THF) was added dropwise via syringe. The resulting mixture was warmed up and stirred for 2 hours at root temperature. It was then quenched with 0.4 mL saturated aqueous NH4Cl. After removing all the solvents in vacuo, the product (4 mg) was obtained as yellow solid through preparative TLC(CH2Cl2/MeOH, v/v, 10:1). ESI MS m/z 455 (M+H). 1H NMR (400 MHz, CD3OD) δ7.61 (s, 1H), 7.48-7.52 (m, 3H), 7.41-7.46 (m, 2H), 7.34-7.40 (m, 1H), 7.24-7.27 (m, 1H), 4.66-4.74 (m, 1H), 4.40 (s, 2H), 4.03 (t, J=8.8 Hz, 1H), 3.96 (dd, J=8.8, 6.8 Hz, 1H), 3.83 (dd, J=12.8, 3.6 Hz, 1H), 3.65 (dd, J=12.8, 3.6 Hz, 1H), 1.96 (s, 3H).

Workup

  1. custom3-[2-Fluoro-4′-(2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazol-2-yl)-biphenyl-4-yl]-5-hydroxymethyl-oxazolidin-2-one was synthesized
  2. customThe flask was flushed with nitrogen
  3. additionwas added 4 mL
  4. customdegassed DMF/H2O (10/1
  5. temperaturewas cooled down
  6. custompartitioned in 60 mL EtOAc/60 mL water
  7. washThe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. customColumn chromatography (CH2Cl2/MeOH, v/v, 20:1 to 10:1) gave impure TBS-
  10. temperaturecooled to 0° C
  11. temperatureThe resulting mixture was warmed up
  12. stirringstirred for 2 hours at root temperature
  13. customIt was then quenched with 0.4 mL saturated aqueous NH4Cl
  14. customAfter removing all the solvents in vacuo

Sources & evidence

ORD record
ord-01d96e31ae194142b49b678459fb0092
Source dataset
uspto-grants-2010_02
Patent number
US07666864B2

Reaction notes

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