Potassium Carbonate → N-{3-[2-Fluoro-4'-(2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazol-2-ylmethoxy)-biphenyl-4-yl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide

HRID 1446068Notes

Reaction equation

HRID 1446068 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][CH:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:27])[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.Br[C:29]1[CH:48]=[CH:47][C:32]([O:33][CH2:34][C:35]2([CH3:46])[O:39][C:38]3=[N:40][C:41]([N+:43]([O-:45])=[O:44])=[CH:42][N:37]3[CH2:36]2)=[CH:31][CH:30]=1.C([O-])([O-])=O.[K+].[K+]>>[F:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][CH:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:27])[CH:5]=[CH:6][C:7]=1[C:29]1[CH:48]=[CH:47][C:32]([O:33][CH2:34][C:35]2([CH3:46])[O:39][C:38]3=[N:40][C:41]([N+:43]([O-:45])=[O:44])=[CH:42][N:37]3[CH2:36]2)=[CH:31][CH:30]=1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 22273985N-{3-[3-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamideHCID 685456062-(4-Bromo-phenoxymethyl)-2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazole

Product 1

HCID 68550244N-{3-[2-Fluoro-4'-(2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazol-2-ylmethoxy)-biphenyl-4-yl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide

Conditions

Temperature
80 °C

Procedure

To an oven dried round bottom flask was charged N-{3-[3-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (78 mg, 0.2 mmol), 2-(4-Bromo-phenoxymethyl)-2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazole (prepared similarly as described by Sasaki, H. et al: Journal of Medicinal Chemistry (2006), 49(26), 7854-7860; 71 mg, 0.2 mmol), Ph(PPh3)4 (23 mg, 0.02 mmol) and K2CO3 (55 mg, 0.4 mmol). The flask was flushed with nitrogen and was added 3 mL degassed DMF/H2O (10/1, v/v). The resulting mixture was stirred at 80° C. for 3 hours before it was cooled down and partitioned into 50 mL EtOAc/50 mL water. The organic layer was washed with brine and dried over Na2SO4, concentrated, and purified by column chromatography (CH2Cl2/MeOH, v/v, 20:1 to 10:1) gave the titled compound (70 mg) as off-white solid. ESI MS m/z 526 (M+H). 1H NMR (400 MHz, CD3OD) δ 7.86 (s, 1H), 7.52-7.59 (m, 1H), 7.45-7.52 (m, 3H), 7.32-7.38 (m, 1H), 6.96-7.02 (m, 2H), 4.76-4.84 (m, 1H), 4.51 (d, J=6.8 Hz, 1H), 4.38 (d, J=6.8 Hz, 1H), 4.27 (d, J=6.8 Hz, 1H), 4.18 (d, J=6.8 Hz, 1H), 3.89 (s, 1H), 3.83 (dd, J=6.8, 9.2 Hz, 1H), 3.55-3.59 (m, 2H), 1.96 (s, 3H), 1.77 (s, 3H).

Workup

  1. customTo an oven dried round bottom flask
  2. customprepared similarly
  3. customThe flask was flushed with nitrogen
  4. additionwas added 3 mL
  5. customdegassed DMF/H2O (10/1
  6. temperaturewas cooled down
  7. custompartitioned into 50 mL EtOAc/50 mL water
  8. washThe organic layer was washed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. custompurified by column chromatography (CH2Cl2/MeOH, v/v, 20:1 to 10:1)

Sources & evidence

ORD record
ord-0be759e07c2c4ac48bafc163b291e7ec
Source dataset
uspto-grants-2010_02
Patent number
US07666864B2

Reaction notes

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