Sodium hydride → HCID 66971860, compound

HRID 1364206Notes

Reaction equation

HRID 1364206 reaction equation
N1[C:5](=O)[CH2:4][CH2:3][C@@H:2]1[C:7](O)=O.[NH2:10][C@@H:11]1[CH2:17][CH2:16][C:15]2[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=2[NH:13][C:12]1=[O:22].[H-].[Na+].[F:25][C:26]([F:37])([F:36])[CH2:27]OS(C(F)(F)F)(=O)=O>C(OCC)(=O)C>[F:25][C:26]([F:37])([F:36])[CH2:27][N:13]1[C:14]2[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=2[CH2:16][CH2:17][C@@H:11]([NH:10][C:2]([C:7]2[CH:5]=[CH:4][CH:3]=[CH:2][CH:7]=2)([C:21]2[CH:14]=[CH:15][CH:18]=[CH:19][CH:20]=2)[C:3]2[CH:12]=[CH:11][CH:17]=[CH:5][CH:4]=2)[C:12]1=[O:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 10881289HCID 10881289, compound

Product 1

HCID 66971860HCID 66971860, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A round-bottom flask containing the product of Step 4 for the preparation of Example 1 (2.00 g, 4.80 mmol) was fitted with a stirbar and septa and flushed with nitrogen. Tetrahydrofuran (20 mL) was added, giving a solution that was cooled to 0° C. Sodium hydride (0.781 g, 60%/oil, 19.5 mmol) was added, and the reaction was stirred for 30 minutes. Trifluoromethanesulfonic acid-2,2,2-trifluoroethyl ester (2.26 g, 9.74 mmol) was then added, and stirring was continued with gradual warming to room temperature. After 18 hours, the reaction mixture was poured into ethyl acetate (75 mL) and washed first with 1:1 H2O:saturated aqueous NaHCO3 solution (2×30 mL), then with saturated aqueous NaCl solution (20 mL). The aqueous wash layers were combined and extracted with ethyl acetate (30 mL). The ethyl acetate layers were then combined, dried over MgSO4, filtered and concentrated in vacuo to give an oil that was purified via flash chromatography on silica gel (5% to 15% ethyl acetate/hexanes linear gradient) to give the desired product.

Workup

  1. customwas fitted with a stirbar and septa
  2. customflushed with nitrogen
  3. additionTetrahydrofuran (20 mL) was added
  4. customgiving a solution that
  5. stirringstirring
  6. temperaturewith gradual warming to room temperature
  7. waitAfter 18 hours
  8. washwashed first with 1:1 H2O
  9. extractionextracted with ethyl acetate (30 mL)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give an oil that
  14. customwas purified via flash chromatography on silica gel (5% to 15% ethyl acetate/hexanes linear gradient)

Sources & evidence

ORD record
ord-005656cbfa584a138bd07b3bc8fb7d2a
Source dataset
uspto-grants-2011_02
Patent number
US07888345B2

Reaction notes

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