4-Methoxyphenol → 4'-(4-methoxyphenoxy)-1'-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 1407927Notes

Reaction equation

HRID 1407927 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:16]3=[CH:17][C:18]4[O:19][CH2:20][CH2:21][O:22][C:23]=4[CH:24]=[C:15]3[O:14][CH2:13]1)[C:5](=[O:12])[N:6]2[CH3:11].[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=1.CC(C)([O-])C.[K+].CN1CCCC1=O>[Cu]Br.O>[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[C:4]2([C:16]4[C:15](=[CH:24][C:23]5[O:22][CH2:21][CH2:20][O:19][C:18]=5[CH:17]=4)[O:14][CH2:13]2)[C:5](=[O:12])[N:6]3[CH3:11])=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 90154-MethoxyphenolHCID 13387N-methyl-2-pyrrolidoneHCID 23665647Potassium tert-butoxideHCID 593527794'-bromo-1'-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1H)-one

Product 1

HCID 593521984'-(4-methoxyphenoxy)-1'-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-oneYield 39%

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 962WaterSolvent

Procedure

A 10 mL microwave reaction vessel was charged with 4′-bromo-1′-methyl-3,7-dihydro-2H-spiro[benzofuro[5,6-b][1,4]dioxine-8,3′-indolin]-2′-one (0.19 g, 0.5 mmol), 4-methoxyphenol (0.12 g, 1.0 mmol), potassium tert-butoxide (0.11 g, 1.0 mmol), copper (I) bromide (0.012 g, 0.08 mmol) and anhydrous 1-methylpyrrolidin-2-one (2 mL). The reaction mixture was irradiated at 250° C. for 75 min in a microwave reactor and was allowed to cool to ambient temperature. The reaction mixture was poured into water (15 mL) and extracted with ethyl acetate (50 mL). The combined organic extracts were washed with water (3×50 mL) and brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification of the residue by column chromatography and eluted with a 15% to 50% gradient of ethyl acetate in hexanes afforded 4′-(4-methoxyphenoxy)-1′-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.084 g, 39%) as an off-white solid: mp 55-58° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ7.27-7.14 (m, 1H), 6.78-6.59 (m, 5H), 6.44 (d, J=8.48 Hz, 1H), 6.31 (d, J=1.08 Hz, 1H), 6.22 (d, J=1.08 Hz, 1H), 4.86 (ABq, 2H), 4.16-4.03 (m, 4H), 3.74 (s, 3H), 3.26 (s, 3H); 13C NMR (75 MHz, CDCl3) δ177.6, 155.8, 155.6, 154.3, 149.6, 144.8, 144.3, 137.7, 130.0, 120.2, 120.1, 119.5, 114.5, 112.7, 111.0, 103.1, 99.1, 64.4, 63.9, 57.4, 55.6, 27.0; MS (ES+) m/z 432.0 (M+1).

Workup

  1. customThe reaction mixture was irradiated at 250° C. for 75 min in a microwave reactor
  2. extractionextracted with ethyl acetate (50 mL)
  3. washThe combined organic extracts were washed with water (3×50 mL) and brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by column chromatography
  8. washeluted with a 15% to 50% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-457314f432294853ae7cfab166c4c366
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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