Sodium hydride → tert-Butyl 4-{1-[2-(5-bromo-2,3-difluorophenyl)-1-(4-chlorophenyl)-2-oxoethyl]butyl}benzoate

HRID 1879633Notes

Reaction equation

HRID 1879633 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:5]([Si](C)(C)C)=[C:6]([F:21])[C:7]([F:20])=[C:8]([C:10](=[O:19])[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH:9]=1.Br[CH:27]([C:31]1[CH:43]=[CH:42][C:34]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:33][CH:32]=1)[CH2:28][CH2:29][CH3:30]>CN(C=O)C.[Na+].[Cl-]>[Br:3][C:4]1[CH:5]=[C:6]([F:21])[C:7]([F:20])=[C:8]([C:10](=[O:19])[CH:11]([CH:27]([C:31]2[CH:43]=[CH:42][C:34]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:33][CH:32]=2)[CH2:28][CH2:29][CH3:30])[C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH:9]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 585380691-[5-Bromo-2,3-difluoro-4-(trimethylsilyl)phenyl]-2-(4-chlorophenyl)ethanoneHCID 67486774Tert-butyl 4-(1-bromobutyl)benzoate

Product 1

HCID 58538054tert-Butyl 4-{1-[2-(5-bromo-2,3-difluorophenyl)-1-(4-chlorophenyl)-2-oxoethyl]butyl}benzoate

Reagents, catalysts & solvents 2

HCID 5234Sodium ChlorideSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of NaH (60 wt % in mineral oil, 0.129 g, 3.23 mmol) in DMF (5 mL) at 0° C. was add a solution of the product from Step D (0.900 g, 2.15 mmol) in DMF (2 mL). The suspension was stirred for 30 minutes, then a solution of tert-butyl 4-(1-bromobutyl)benzoate (0.742 g, 2.37 mmol) in DMF (2 mL) was added. The mixture was stirred at 0° C. for two hours then diluted with saturated NaCl (aq, 50 mL), then the product was extracted with EtOAc (3×30 mL). The combined organic extracts were washed with water then saturated NaCl (aq), dried over MgSO4, filtered, then concentrated. The resulting residue was purified by silica gel chromatography eluting with 0-50% toluene/hexanes to afford racemic mixtures of both diastereomers of the title compound.

Workup

  1. stirringThe mixture was stirred at 0° C. for two hours
  2. extractionthe product was extracted with EtOAc (3×30 mL)
  3. washThe combined organic extracts were washed with water
  4. dry with materialsaturated NaCl (aq), dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica gel chromatography
  8. washeluting with 0-50% toluene/hexanes

Sources & evidence

ORD record
ord-2c68047ae8144e36ab75a82c423a18e3
Source dataset
uspto-grants-2012_11
Patent number
US08318667B2

Reaction notes

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