Bromide ion → 5-[3-(Tert-butyl-dimethyl-silanyloxy)-phenyl]-5-oxo-pentanoic acid

HRID 1060891Notes

Reaction equation

HRID 1060891 reaction equation
[Mg].Br[C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][CH:16]=1)[O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[Br-].[C:18]1(=[O:25])[O:24][C:22](=[O:23])[CH2:21][CH2:20][CH2:19]1>C1COCC1.CCOC(C)=O>[C:10]([Si:7]([CH3:9])([CH3:8])[O:6][C:5]1[CH:4]=[C:3]([C:18](=[O:25])[CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])[CH:16]=[CH:15][CH:14]=1)([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 259Bromide ionHCID 7940Glutaric anhydrideHCID 5462224MagnesiumHCID 11254705(3-Bromophenoxy)(tert-butyl)dimethylsilane

Product 1

HCID 186294385-[3-(Tert-butyl-dimethyl-silanyloxy)-phenyl]-5-oxo-pentanoic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Magnesium (0.226 g, 8.58 mmol) was flame dried in a 50 mL RB flask equipped with addition funnel and magnetic stirrer under N2. When the flask had cooled, anhydrous THF (25 mL), a pinch of iodine, and a THF solution of Rieke magnesium (1 mL) were added, followed by a small portion of 3-bromophenoxy-tert-butyl(dimethyl)silane (2.24 g, 7.80 mmol) in THF (3 mL) with slight warming to initiate the reaction. The remainder of the bromide solution (10 mL) was added dropwise over 15 min. After 0.5 h this Grignard solution was added to a solution of glutaric anhydride (0.89 g, 7.8 mmol) in THF (10 mL) with cooling in an ice-H2O bath. After 2 h, the reaction mixture was diluted with EtOAc and washed with 1N NaOH (5×) to extract the product. The aqueous basic solution was cooled in an ice-H2O bath and acidified with 12N HCl, then extracted with CH2Cl2 (3×50 mL). The organic layers were combined, washed with brine, dried (MgSO4), filtered and concentrated to give the crude product. Purification on an ISCO Combiflash eluting with 3-7% MeOH/CH2Cl2 w/NH4OH gave the title compound. MS(M+1)323.

Workup

  1. customdried in a 50 mL RB flask
  2. customequipped with addition funnel and magnetic stirrer under N2
  3. temperatureWhen the flask had cooled
  4. additionanhydrous THF (25 mL), a pinch of iodine, and a THF solution of Rieke magnesium (1 mL) were added
  5. temperaturewith slight warming
  6. customthe reaction
  7. temperaturewith cooling in an ice-H2O bath
  8. washwashed with 1N NaOH (5×)
  9. extractionto extract the product
  10. temperatureThe aqueous basic solution was cooled in an ice-H2O bath
  11. extractionextracted with CH2Cl2 (3×50 mL)
  12. washwashed with brine
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customto give the crude product
  17. customPurification on an ISCO Combiflash
  18. washeluting with 3-7% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-67cb62fea9a6457bb5e75f45df7ea828
Source dataset
uspto-grants-2003_02
Patent number
US06525074B2

Reaction notes

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