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

HRID 1297803Notes

Reaction equation

HRID 1297803 reaction equation
[Si:1]([O:8][C:9]1[C:14]([CH3:15])=[CH:13][C:12]([C:16]2(O)[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].[CH3:28][O:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1.C(N(CC)CC)C>ClCCl.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]([CH:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([C:34]3[CH:33]=[CH:32][CH:31]=[C:30]([O:29][CH3:28])[CH:35]=3)[C:17]2=[O:25])=[CH:13][C:14]=1[CH3:15])([CH3:5])([CH3:7])[CH3:6]

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 2734370(3-Methoxyphenyl)boronic acid2×HCID 589146893-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one

Product 1

HCID 695232033-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1-(3-methoxy-phenyl)-1,3-dihydro-indol-2-oneYield 50.7%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

Combine 3-[4-(tert-Butyl-dimethylsilanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one (15.34 g, 40 mmol), 3-methoxyphenylboronic acid (12.16 g, 80 mmol), copper (II) acetate (7.27 g, 40 mmol), triethyl amine (11.2 ml, 80 mmol) and 4A sieves (100 g) in dichloromethane (1 L) and heat at 32° C. for 1 day stirring mechanically. Add more 3-methoxyphenylboronic acid (6.0 g, 39 mmol), copper (II) acetate (7.27 g, 40 mmol), triethyl amine (5.6 ml, 40 mmol) and 4A sieves (50 g) and continue heating for 3 days. Filter the reaction through Celite washing liberally with dichloromethane. Add ethyl acetate to get more precipitate and refilter through Celite. Evaporate in vacuo to obtain an oil of about 30 g. Purify by preparative HPLC (gradient of 15% ethyl acetate/dichloromethane to 50% ethyl acetate/dichloromethane) to obtain 9.60 g of an orange foam. MS (ES): m/z=490 (M+1); 1H NMR (DMSO-d6); δ7.50 (t, 1H), 7.28-7.23 (m, 2H), 7.12-6.98 (m, 6H), 6.82 (d, 1H), 6.72 (s, 1H), 3.81 (s, 3H), 2.14 (s, 6H), 0.99 (s, 9H), 0.17 (s, 6H).

Workup

  1. temperaturecontinue heating for 3 days
  2. filtrationFilter
  3. customthe reaction through Celite
  4. washwashing liberally with dichloromethane
  5. customAdd ethyl acetate to get more precipitate and refilter through Celite
  6. customEvaporate in vacuo
  7. customto obtain an oil of about 30 g
  8. customPurify by preparative HPLC (gradient of 15% ethyl acetate/dichloromethane to 50% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-e00f78b897ef42b590d28fa635dfec77
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

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