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

HRID 1297805Notes

Reaction equation

HRID 1297805 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].[C:28]1([CH3:37])[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=1.N1C=CC=CC=1>ClCCl.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:30]3[CH:29]=[C:28]([CH3:37])[CH:33]=[CH:32][CH:31]=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 27339503-Tolylboronic acid2×HCID 589146893-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one

Product 1

HCID 589147163-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1-m-tolyl-1,3-dihydro-indol-2-oneYield 123.5%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolventHCID 21226138Dichloromethane ethylacetateSolvent

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 (11.51 g, 30 mmol), m-tolylboronic acid (8.16 g, 60 mmol), copper (II) acetate (5.45 g, 30 mmol), pyridine (4.9 ml, 60 mmol) and powdered 4A sieves (15 g) in dichloromethane (100 mL) and heat at 32° C. for 1 day stirring mechanically. Add more m-tolylboronic acid (4.08 g, 30 mmol), copper (II) acetate (2.73 g, 15 mmol), pyridine (5.0 ml, 62 mmol) and powdered 4A sieves (15 g) and continue heating for 1 day. Dilute with dichloromethane/ethyl acetate and filter slowly through a pad of Celite and silica gel. Use three such pads to filter the entire reaction washing liberally with ethyl acetate. After the filtration is complete stir the pads in additional ethyl acetate and refilter. Evaporate the organics in vacuo to obtain 17.55 g of a yellow oil. Purify by preparative HPLC (5% ethyl acetate/hexanes for 5 minutes and then use gradient up to 25% ethyl acetate/hexanes) to obtain 9.05 g (64%) of a yellow gum. MS (ES): m/z=474 (M+1); 1H NMR (DMSO-d6); δ7.47 (t, 1H), 7.30-7.23 (m, 5H), 7.09 (t, 1H), 6.77 (d, 1H), 6.72 (s, 1H), 2.39 (s, 3H), 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 pad of Celite and silica gel
  4. filtrationto filter
  5. customthe entire reaction
  6. washwashing liberally with ethyl acetate
  7. filtrationAfter the filtration
  8. stirringis complete stir the pads in additional ethyl acetate
  9. customEvaporate the organics in vacuo

Sources & evidence

ORD record
ord-b0bd87bae6a54e929d34809010d5c959
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

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