Cesium carbonate → 1'-[(3-isopropylisoxazol-5-yl)methyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

HRID 2385145Notes

Reaction equation

HRID 2385145 reaction equation
[CH:1]([C:4]1[CH:8]=[C:7]([CH2:9]O)[O:6][N:5]=1)([CH3:3])[CH3:2].[Cl-].ClC=[N+](C)C.[NH:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]2([C:29]3=[CH:30][C:31]4[O:35][CH2:34][O:33][C:32]=4[CH:36]=[C:28]3[O:27][CH2:26]2)[C:18]1=[O:37].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH:1]([C:4]1[CH:8]=[C:7]([CH2:9][N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]3([C:29]4=[CH:30][C:31]5[O:35][CH2:34][O:33][C:32]=5[CH:36]=[C:28]4[O:27][CH2:26]3)[C:18]2=[O:37])[O:6][N:5]=1)([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 14439316(3-(Propan-2-yl)-1,2-oxazol-5-yl)methanolHCID 53375495spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

Product 1

HCID 685972191'-[(3-isopropylisoxazol-5-yl)methyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneYield 61.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To an ice-cold stirring suspension of (3-isopropylisoxazol-5-yl)methanol (0.338 g, 2.4 mmol) in N,N-dimethylformamide (20 mL) was added a solution of N-(chloromethylene)-N-methylmethanaminium chloride (0.36 g, 2.8 mmol) in N,N-dimethylformamide (10 mL). The mixture was stirred at ambient temperature for 30 min and then transferred to a suspended mixture of spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.56 g, 2.0 mmol), cesium carbonate (1.95 g, 6.0 mmol) in N,N-dimethylformamide (4 mL). The reaction mixture was stirred at ambient temperature for 16 h and filtered. The solid was washed with acetone (100 mL). The filtrate was concentrated in vacuo. The residue was purified by column chromatography with ethyl acetate in hexanes (10% to 30% gradient) to give 1′-[(3-isopropylisoxazol-5-yl)methyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.50 g, 60%) as a colorless solid: mp 132-136° C. (diethyl ether/hexanes); 1H NMR (300 MHz, DMSO-d6) 87.34 (ddd, J=7.7, 7.7, 1.2 Hz, 1H), 7.21 (d, J=7.5 Hz, 1H), 7.14 (d, J=7.7 Hz, 1H), 7.08 (ddd, J=7.5, 7.5, 0.8 Hz, 1H), 6.71 (s, 1H), 6.49 (s, 1H), 6.21 (s, 1H), 5.93 (d, J=1.0 Hz, 2H), 5.08 (s, 2H), 4.82 (d, J=9.4 Hz, 1H), 4.72 (d, J=9.4 Hz, 1H), 3.03 (m, 1H), 1.19 (d, J=6.9 Hz, 6H); 13C NMR (75 MHz, DMSO-d6) δ176.4, 168.9, 166.3, 155.2, 148.3, 141.6, 141.5, 131.4, 128.8, 123.6, 123.2, 119.5, 109.1, 102.8, 101.3, 101.1, 93.2, 79.5, 57.2, 35.6, 25.8, 21.2; MS (ES+) m/z 405.3 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 16 h
  2. filtrationfiltered
  3. washThe solid was washed with acetone (100 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by column chromatography with ethyl acetate in hexanes (10% to 30% gradient)

Sources & evidence

ORD record
ord-6a90c5b2b14240329a54da1325b09e55
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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