Sodium Carbonate → ethyl 3-(4-{[4-(4-{[tert-butyl(dimethyl)silyl]oxy}-2,6-dimethylphenyl)-2,3-dihydro-1H-inden-1-yl][(2-nitrophenyl)sulfonyl]amino}-2-fluorophenyl)propanoate

HRID 508095Notes

Reaction equation

HRID 508095 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]([S:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[N+:35]([O-:37])=[O:36])(=[O:28])=[O:27])[CH:9]2[C:17]3[C:12](=[C:13](OS(C(F)(F)F)(=O)=O)[CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10]2)[CH:5]=[CH:4][C:3]=1[CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41].[Si:45]([O:52][C:53]1[CH:58]=[C:57]([CH3:59])[C:56](B(O)O)=[C:55]([CH3:63])[CH:54]=1)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46].C(=O)([O-])[O-].[Na+].[Na+]>O.C(O)C.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Si:45]([O:52][C:53]1[CH:58]=[C:57]([CH3:59])[C:56]([C:13]2[CH:14]=[CH:15][CH:16]=[C:17]3[C:12]=2[CH2:11][CH2:10][CH:9]3[N:8]([S:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[N+:35]([O-:37])=[O:36])(=[O:28])=[O:27])[C:6]2[CH:5]=[CH:4][C:3]([CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:2]([F:1])[CH:7]=2)=[C:55]([CH3:63])[CH:54]=1)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 23157502HCID 23157502, compoundHCID 598383324-[(Tert-butyldimethylsilyl)oxy]-2,6-dimethylphenylboronic acid

Product 1

HCID 68720751ethyl 3-(4-{[4-(4-{[tert-butyl(dimethyl)silyl]oxy}-2,6-dimethylphenyl)-2,3-dihydro-1H-inden-1-yl][(2-nitrophenyl)sulfonyl]amino}-2-fluorophenyl)propanoate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

Ethyl 3-{2-fluoro-4-[[(2-nitrophenyl)sulfonyl](4-{[(trifluoromethyl)sulfonyl]oxy}-2,3-dihydro-1H-inden-1-yl)amino]phenyl}propanoate (3.14 g, 4.76 mmol), (4-{[tert-butyl(dimethyl)silyl]oxy}-2,6-dimethylphenyl)boronic acid (2.0 g, 7.14 mmol) and sodium carbonate (1.51 g, 14.3 mmol) were dissolved in a mixture of water (10 mL), ethanol (10 mL) and toluene (30 mL), and the air was substituted with argon gas. Tetrakis(triphenylphosphine)palladium(0) (0.275 g, 0.24 mmol) was added. The reaction mixture was stirred under an argon atmosphere at 120° C. for 16 hr. After cooling, the reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (3%-60% ethyl acetate/hexane) to give ethyl 3-(4-{[4-(4-{[tert-butyl(dimethyl)silyl]oxy}-2,6-dimethylphenyl)-2,3-dihydro-1H-inden-1-yl][(2-nitrophenyl)sulfonyl]amino}-2-fluorophenyl)propanoate as a yellow oil. The obtained oil was dissolved in tetrahydrofuran (30 mL), tetrabutylammonium fluoride (1 M THF solution, 2.43 mL, 2.43 mmol) was added under stirring at room temperature, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (10%-60% ethyl acetate/hexane) to give the title compound (1.46 g, yield 78%, 2 steps) as a yellow oil.

Workup

  1. temperatureAfter cooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (3%-60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d24875c9c7cf49108b3d3f90b03fdcfe
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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