Isatin → 3-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one

HRID 1297774Notes

Reaction equation

HRID 1297774 reaction equation
Br[C:2]1[CH:15]=[C:14]([CH3:16])[C:5]([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])=[C:4]([CH3:17])[CH:3]=1.C([Li])CCC.CCCCCC.[NH:29]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:32](=[O:33])[C:30]1=[O:31].[NH4+].[Cl-]>C1COCC1>[C:10]([Si:7]([CH3:9])([CH3:8])[O:6][C:5]1[C:14]([CH3:16])=[CH:15][C:2]([C:32]2([OH:33])[C:34]3[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=3)[NH:29][C:30]2=[O:31])=[CH:3][C:4]=1[CH3:17])([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 5

HCID 7054IsatinHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 14959500(4-Bromo-2,6-dimethylphenoxy)(tert-butyl)dimethylsilaneHCID 178418339Butyllithium

Product 1

HCID 589146893-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-oneYield 154.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

Dissolve (4-bromo-2,6-dimethyl-phenoxy)-tert-butyl-dimethyl-silane (15.77 g, 50 mmol) in anhydrous THF (250 mL) under nitrogen and cool in a dry ice/acetone bath. Add slowly at −75 to −70° C. 1.6M n-butyl lithium in hexane (31.3 mL, 55 mmol). Stir the resulting white precipitate at −75° C. for 30 min. Add isatin (3.68 g, 25 mmol) as a solid while maintaing positive nitrogen pressure. Remove some dry ice and allow the reaction to warm up slowly to −30 to −40° C. over 3 h and then to 15° C. over 1 h. Pour the reaction into NH4Cl solution and wash with EtOAc (2×500 mL, 250 mL). Wash combined organic portions with water (500 mL) and brine (500 mL). Dry (MgSO4), filter and concentrate in vacuo to give 14.8 g of a yellow solid. Triturate in hexane/ether/CH2Cl2, filter and air dry to give 6.0 g (63%) of the title compound as a pale yellow solid. MS (ES): m/z=383 (M−1); 1H NMR(DMSO-d6): δ10.14 (s, 1H), 7.07 (dt, J=1.1 Hz, J=7.6 Hz, 1H), 6.95 (d, J=7.0, 1H), 6.80 (t, J=7.3 Hz, 1H), 6.72 (m, 3H), 6.27 (s, 1H), 1.95 (s, 6H), 0.83 (s, 9H), 0.00 (s, 6H).

Workup

  1. temperaturecool in a dry ice/acetone bath
  2. additionAdd slowly at −75 to −70° C
  3. customRemove some dry ice
  4. customthe reaction
  5. temperatureto warm up slowly to −30 to −40° C. over 3 h
  6. waitto 15° C. over 1 h
  7. additionPour
  8. washwash with EtOAc (2×500 mL, 250 mL)
  9. washWash
  10. dry with materialDry (MgSO4)
  11. filtrationfilter
  12. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-c64dec9fd60b4efdac04508fc8951a24
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

Loading…