Cesium carbonate → HCID 59352128, compound

HRID 1965455Notes

Reaction equation

HRID 1965455 reaction equation
[OH:1][C:2]1([C:23]2[C:32]([OH:33])=[CH:31][C:26]3[O:27][CH2:28][CH2:29][O:30][C:25]=3[CH:24]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][C:12]2[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[CH:14][N:13]=2)[C:3]1=[O:22].Cl[CH2:35]I.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1>[F:19][C:18]([F:20])([F:21])[C:17]1[C:12]([CH2:11][N:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]3([C:23]4[CH:24]=[C:25]5[O:30][CH2:29][CH2:28][O:27][C:26]5=[CH:31][C:32]=4[O:33][CH2:35][O:1]3)[C:3]2=[O:22])=[N:13][CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11644ChloroiodomethaneHCID 67357306HCID 67357306, compound

Product 1

HCID 59352128HCID 59352128, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 100 mL flask was charged under argon with 3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1-{[3-(trifluoromethyl)pyridine-2-yl]methyl}-1,3-dihydro-2H-indol-2-one (0.46 g, 1.0 mmol), chloroiodomethane (0.36 g, 2.0 mmol), cesium carbonate (1.3 g, 4.0 mmol) and anhydrous tetrahydrofuran (50 mL). The reaction mixture was heated at reflux for 3 h, allowed to cool to ambient temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography and eluted with a 0% to 50% gradient of ethyl acetate in dichloromethane to afford 1′-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-7,8-dihyrdospiro[1,4-dioxino[2,3-g][1,3]benzodioxine-4,3′-indol]-2′(1H)-one (0.16 g, 34%) as an off-white solid: mp>250° C. (methanol); 1H NMR (300 MHz, CDCl3) δ 8.65 (d, J=4.5 Hz, 1H), 7.96 (d, J=7.8 Hz, 1H), 7.35-7.14 (m, 3H), 6.95-7.03 (m, 1H), 6.68 (s, 1H), 6.57 (d, J=7.8 Hz, 1H), 6.52 (s, 1H), 5.70 (ABq, 2H), 5.21 (ABq, 2H), 4.25-4.01 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 176.3, 152.3, 152.2, 147.8, 144.1, 143.3, 138.9, 134.3, 134.2, 134.2, 134.1, 130.7, 130.2, 129.2, 125.6, 125.2, 124.8, 124.4, 124.0, 123.5, 122.2, 122.0, 114.9, 114.2, 108.7, 105.3, 88.3, 77.2, 64.5, 64.0, 41.8, 41.7.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 h
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by column chromatography
  6. washeluted with a 0% to 50% gradient of ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-c7197085e66b45699338967e66e9f330
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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