Triphenylphosphine → ethyl 3-(2-fluoro-4-{(4-hydroxy-2,3-dihydro-1H-inden-1-yl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate

HRID 507996Notes

Reaction equation

HRID 507996 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24].[Si]([O:35][C:36]1[CH:44]=[CH:43][CH:42]=[C:41]2[C:37]=1[CH2:38][CH2:39][CH:40]2O)(C(C)(C)C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([N:8]([CH:40]2[C:41]3[C:37](=[C:36]([OH:35])[CH:44]=[CH:43][CH:42]=3)[CH2:38][CH2:39]2)[S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])(=[O:10])=[O:11])[CH:5]=[CH:4][C:3]=1[CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24]

Participants

8

Reactant 5

HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 2724141Tetrabutylammonium FluorideHCID 23157368Ethyl 3-(2-fluoro-4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoateHCID 594341364-{[Tert-butyl(dimethyl)silyl]oxy}indan-1-ol2×

Product 1

HCID 23157538ethyl 3-(2-fluoro-4-{(4-hydroxy-2,3-dihydro-1H-inden-1-yl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoateYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 3-(2-fluoro-4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (20.0 g, 50.5 mmol), 4-{[tert-butyl(dimethyl)silyl]oxy}indan-1-ol (14.7 g, 55.6 mmol) and triphenylphosphine (14.6 g, 55.6 mmol) in tetrahydrofuran (300 mL) was stirred under ice-cooling, and diethyl azodicarboxylate (40% toluene solution, 25.3 mL, 55.6 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 16 hr. To the reaction mixture were added reagents (4-{[tert-butyl(dimethyl)silyl]oxy}indan-1-ol, triphenylphosphine and diethyl azodicarboxylate) in a half amount of the above, and the mixture was further stirred for 4 hr. The reaction mixture was concentrated, and diethyl ether and hexane were added to the residue. The resultant insoluble material was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5-hexane/ethyl acetate=30/70) to give a yellow oil. To a solution of the obtained oil in tetrahydrofuran (250 mL) was added tetrabutylammonium fluoride (1 M THF solution, 61.1 mL, 61.1 mmol) under stirring under ice cooling and the mixture was stirred at the same temperature for 3 hr. Ethyl acetate was added to the reaction mixture, and the mixture was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=70/30-hexane/ethyl acetate=30/70) to give the title compound (21.5 g, yield 81%, 2 steps) as a yellow oil.

Workup

  1. temperaturecooling
  2. stirringwas further stirred for 4 hr
  3. concentrationThe reaction mixture was concentrated
  4. additiondiethyl ether and hexane were added to the residue
  5. filtrationThe resultant insoluble material was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5-hexane/ethyl acetate=30/70)
  8. customto give a yellow oil
  9. stirringunder stirring under ice cooling
  10. stirringthe mixture was stirred at the same temperature for 3 hr
  11. washthe mixture was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=70/30-hexane/ethyl acetate=30/70)

Sources & evidence

ORD record
ord-2cf43b7a7f944375b42d0e353f5d058b
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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