Cesium carbonate → 1'-(diphenylmethyl)-5,6-difluorospiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

HRID 2385038Notes

Reaction equation

HRID 2385038 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:10]2=[O:31])=[C:4]([OH:32])[CH:3]=1.[C:33](=O)([O-])[O-].[Cs+].[Cs+].ClCI>O1CCCC1>[C:19]1([CH:18]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:9]3([C:5]4[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=4[O:32][CH2:33]3)[C:10]2=[O:31])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11644ChloroiodomethaneHCID 673572403-(4,5-difluoro-2-hydroxyphenyl)-1-(diphenylmethyl)-1,3-dihydro-2H-indol-2-one

Product 1

HCID 593520761'-(diphenylmethyl)-5,6-difluorospiro[1-benzofuran-3,3'-indol]-2'(1'H)-oneYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4,5-difluoro-2-hydroxyphenyl)-1-(diphenylmethyl)-1,3-dihydro-2H-indol-2-one (6.30 g, 14.7 mmol) in anhydrous tetrahydrofuran (120 mL) under argon was added cesium carbonate (14.4 g, 44.2 mmol), followed by the addition of chloroiodomethane (3.21 mL, 44.2 mmol) dropwise. After 20 h, the reaction mixture was concentrated in vacuo and re-dissolved in ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (6×50 mL). Some product was filtered off as a colorless precipitate. The combined organic solution was washed with water (2×150 mL) and brine (150 mL), dried over sodium sulfate, filtered, and concentrated. Precipitation from diethyl ether/hexanes afforded 1′-(diphenylmethyl)-5,6-difluorospiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (4.51 g, 70%) as a colorless solid: mp 213-216° C.; 1H NMR (300 MHz, CDCl3) δ 7.41-7.26 (m, 10H), 7.15-7.12 (m, 1H), 7.08-6.97 (m, 3H), 6.78 (dd, J=10.5, 6.3 Hz, 1H), 6.54 (d, J=8.4 Hz, 1H), 6.44 (dd, J=9.0, 7.8 Hz, 1H), 5.03 (d, J=9.0 Hz, 1H), 4.77 (d, J=9.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 176.8, 156.6 (d, J=11.0 Hz), 151.2 (dd, JC-F=248.2, 14.5 Hz), 145.6 (dd, JC-F=241.5, 13.85 Hz), 141.7, 137.4, 137.1, 131.5, 128.8, 128.8, 128.7, 128.3, 128.3, 128.1, 128.0, 124.2 (dd, J=6.4, 3.3 Hz), 123.8, 123.3, 112.4, 111.5 (dd, J=20.4, 1.6 Hz), 100.1 (d, J=22.4), 80.8, 58.9, 57.5; MS (ES+) m/z 440.2 (M+1), 462.2 (M+23).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionre-dissolved in ethyl acetate (50 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (6×50 mL)
  4. filtrationSome product was filtered off as a colorless precipitate
  5. washThe combined organic solution was washed with water (2×150 mL) and brine (150 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPrecipitation from diethyl ether/hexanes

Sources & evidence

ORD record
ord-c354afe2c1784089b56641abc64800c2
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

Loading…