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

HRID 1297806Notes

Reaction equation

HRID 1297806 reaction equation
[Si:1]([O:8][C:9]1[C:14]([CH3:15])=[CH:13][C:12]([C:16]2([OH:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][C:17]2=[O:25])=[CH:11][C:10]=1[CH3:27])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:28][C:29]([F:41])([F:40])[O:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.N1C=CC=CC=1>ClCCl.C(OCC)(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:4]([Si:1]([CH3:3])([CH3:2])[O:8][C:9]1[C:10]([CH3:27])=[CH:11][C:12]([C:16]2([OH:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([O:30][C:29]([F:28])([F:40])[F:41])[CH:32]=3)[C:17]2=[O:25])=[CH:13][C:14]=1[CH3:15])([CH3:6])([CH3:5])[CH3:7]

Participants

7

Reactant 3

HCID 1049Pyridine2×HCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)2×HCID 589146893-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one

Product 1

HCID 589147333-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1-(3-trifluoromethoxy-phenyl)-1,3-dihydro-indol-2-oneYield 80.2%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
32 °C

Procedure

Using a method similar to Preparation 38, with 3-[4-(tert-Butyl-dimethylsilanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one (15.34 g, 40 mmol), 3-(trifluoromethoxy)phenylboronic acid (16.47 g, 80 mmol), copper (II) acetate (7.27 g, 40 mmol), pyridine (6.5 ml, 80 mmol) and powdered 4A sieves (25 g) in dichloromethane (130 mL) and heat at 32° C. for 1 day stirring mechanically. Add more 3-(trifluoromethoxy)phenylboronic acid (8.24 g, 40 mmol), copper (II) acetate (3.64 g, 20 mmol), pyridine (6.5 ml, 80 mmol) and powdered 4A sieves (25 g) and continue heating for 1 day. Dilute with ethyl acetate (150 mL) and filter slowly through a pads of Celite and silica gel. After the filtration is complete stir the pads in additional ethyl acetate and refilter. Evaporate the organics in vacuo and apply the resulting residue to a silica pad with dichloromethane/acetone. Elute with 2% ethyl acetate/dichloromethane and concentrate in vacuo to obtain 17.45 g of a yellow solid. Titurate the solid in diethyl ether, filter, and dry to obtain 9.47 g (44%) of a white solid. MS (ES): m/z=526 (M+1−H2O); 1H NMR (DMSO-d6): δ7.71 (t, 1H), 7.58-7.52 (m, 3H), 7.32-7.25 (m, 2H), 7.13 (t, 1H), 7.01 (s, 2H), 6.87 (d, 1H), 6.76 (s, 1H), 2.14 (s, 6H), 0.99 (s, 9H), 0.17 (s, 6H).

Workup

  1. customsimilar to Preparation 38
  2. temperaturecontinue heating for 1 day
  3. filtrationfilter slowly through a pads of Celite and silica gel
  4. filtrationAfter the filtration
  5. stirringis complete stir the pads in additional ethyl acetate
  6. customEvaporate the organics in vacuo
  7. washElute with 2% ethyl acetate/dichloromethane
  8. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-ec7064a55b8044588727b664b9f444b6
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

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