Sodium hydride → HCID 53786148, compound

HRID 1939836Notes

Reaction equation

HRID 1939836 reaction equation
[CH3:1][O:2][N:3]=[C:4]([CH:7]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][C:13]([OH:22])([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)[CH2:5][OH:6].[H-].[Na+].[F:33][C:34]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:35]=1[CH2:36]Br>CN(C=O)C>[CH3:1][O:2][N:3]=[C:4]([CH:7]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][C:13]([OH:22])([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)[CH2:5][O:6][CH2:36][C:35]1[CH:38]=[CH:39][C:40]([F:42])=[CH:41][C:34]=1[F:33]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 54338219HCID 54338219, compound

Product 1

HCID 53786148HCID 53786148, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Treat a solution of the hydroxy-oxime (200 mg, 0.44 mmol) of Step 4 in DMF at 0° C. with NaH (12 mg, 0.48 mmol). Stir the resulting mixture for 30 mins at 0° C. Add 2,4-difluorobenzylbromide (60 μL, 0.465 mmol) in one portion and remove cooling bath. Stir the reaction for 12-18 hours at room temperature. Quench the reaction with H2O and extract with EtOAC (3×30 mL). Dry the combined organic layers over MgSO4, filter and concentrate under reduced pressure to give the crude compound as a yellow oil. Purify by silica gel chromatography (column: 2.5 cm×15 cm; pack column in 50% EtOAc/Hexane and elute using a gradient of 50-100% EtOAc/Hexane) to obtain 128 mg (0.22 mmol, 50% ) of the title compound as a pale oil. HRMS (FAB, M+H+): m/e cal'd for [C30H33N2O3Cl2F2 ]+ : 577.1836, found 577.1832.

Workup

  1. temperaturecooling bath
  2. stirringStir
  3. customthe reaction for 12-18 hours at room temperature
  4. customQuench
  5. customthe reaction with H2O
  6. extractionextract with EtOAC (3×30 mL)
  7. dry with materialDry the combined organic layers over MgSO4
  8. filtrationfilter
  9. concentrationconcentrate under reduced pressure
  10. customto give the crude compound as a yellow oil
  11. customPurify by silica gel chromatography (column
  12. washpack column in 50% EtOAc/Hexane and elute

Sources & evidence

ORD record
ord-70432b3b27f042f980d88cb2f990864d
Source dataset
uspto-grants-1997_12
Patent number
US05696267

Reaction notes

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