Hydrochloric Acid → HCID 58914705, compound

HRID 1297777Notes

Reaction equation

HRID 1297777 reaction equation
C([Si](C)(C)[O:6][C:7]1[C:12]([CH3:13])=[CH:11][C:10]([CH:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[Cl:30])[C:15]2=[O:31])=[CH:9][C:8]=1[CH3:32])(C)(C)C.[CH3:35][Si]([N-][Si](C)(C)C)(C)C.[K+].IC.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Cl>CN(C=O)C>[Cl:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[CH2:23][N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14]([C:10]2[CH:9]=[C:8]([CH3:32])[C:7]([OH:6])=[C:12]([CH3:13])[CH:11]=2)([CH3:35])[C:15]1=[O:31]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 2724141Tetrabutylammonium FluorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 58914697HCID 58914697, compound

Product 1

HCID 58914705HCID 58914705, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dissolve 3-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1-(2-chloro-benzyl)-1,3-dihydro-indol-2-one (150 mg, 0.31 mmol) in anhydrous DMF (3 mL) under nitrogen and cool in an ice bath. Add a 0.5M solution of potassium bis(trimethylsilyl)amide (0.622 mL, 0.31 mmol) and stir 10 min. Add iodomethane (0.020 mL, 0.31 mmol) and after 30 min remove the ice bath and allow the reaction to warm to room temperature. After 2.5 h treat the reaction with a 1.0M solution of tetrabutylammonium fluoride (0.35 mL, 0.35 mmol) and stir 2 h. Pour the reaction into 1N HCl (20 mL) and extract with ethyl acetate (3×20 mL). Wash the combined organic portions with brine, dry (MgSO4), filter and concentrate in vacuo to obtain a crude orange oil. Purify by flash chromatography (gradient of 5% EtOAc/hexanes to 33% EtOAc/hexanes) to give 70 mg (58%) of the title compound as a pink solid. MS (ES): m/z=392 (M+1), 390 (M−1); 1H NMR(DMSO-d6): δ8.23 (s, 1H), 7.54 (dd, J=1.9, 1.5 Hz, J=7.5, 7.3 Hz, 1H), 7.38-7.20 (m, 4H), 7.09-7.02 (m, 2H), 6.89 (d, J=7.6 Hz, 1H), 6.80 (s, 2H), 5.02 (s, 2H), 2.11 (s, 6H), 1.70 (s, 3H).

Workup

  1. temperaturecool in an ice bath
  2. customthe reaction
  3. additionAfter 2.5 h treat
  4. stirringstir 2 h
  5. additionPour
  6. extractionextract with ethyl acetate (3×20 mL)
  7. washWash the combined organic portions with brine
  8. dry with materialdry (MgSO4)
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customto obtain a crude orange oil
  12. customPurify by flash chromatography (gradient of 5% EtOAc/hexanes to 33% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e713e6b2a06b4c9fa9c6eb7d227af9ca
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

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