Dichloromethane → 2-(4'-bromo-5,6-difluoro-2'-oxospiro[1-benzofuran-3,3'-indol]-1'(2' H)-yl)-N-(2-fluorophenyl)acetamide

HRID 1259731Notes

Reaction equation

HRID 1259731 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:19]3[CH:20]=[C:21]([F:25])[C:22]([F:24])=[CH:23][C:18]=3[O:17][CH2:16]1)[C:5](=[O:15])[N:6]2[CH2:11][C:12]([OH:14])=O.C(Cl)(=O)C(Cl)=O.[F:32][C:33]1[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=1[NH2:35].ClCCl>C1(C)C=CC=CC=1.CN(C=O)C>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:19]3[CH:20]=[C:21]([F:25])[C:22]([F:24])=[CH:23][C:18]=3[O:17][CH2:16]1)[C:5](=[O:15])[N:6]2[CH2:11][C:12]([NH:35][C:34]1[CH:36]=[CH:37][CH:38]=[CH:39][C:33]=1[F:32])=[O:14]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 95842-FluoroanilineHCID 65578Oxalyl chlorideHCID 66641960(4'-bromo-5,6-difluoro-2'-oxospiro[1-benzofuran-3,3'-indol]-1'(2'H)-yl)acetic acid

Product 1

HCID 592635092-(4'-bromo-5,6-difluoro-2'-oxospiro[1-benzofuran-3,3'-indol]-1'(2' H)-yl)-N-(2-fluorophenyl)acetamideYield 77.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolvent

Procedure

To a solution of (4′-bromo-5,6-difluoro-2′-oxospiro[1-benzofuran-3,3′-indol]-1′(2′H)-yl)acetic acid (0.24 g, 0.59 mmol) and oxalyl chloride (0.15 mL, 1.76 mmol) in toluene (7.00 mL) was added one drop of DMF and the resulted mixture was stirred at ambient temperature overnight. The mixture was concentrated under vacuum. The residue was dissolved in dichloromethane (5.00 mL) and 2-fluoroaniline (0.18 mL, 1.89 mmol) was added at ambient temperature. The mixture was stirred at ambient temperature for one hour. More dichloromethane (100 mL) was added. The organic layer was washed with water, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/5) to give the title compound (0.23 g, 76%): 1H NMR (300 MHz, CDCl3) δ 8.20 (t, 1H), 7.80 (br, 1H), 7.27-7.17 (m, 2H), 7.16-7.03 (m, 3H), 6.97-6.88 (m, 1H), 6.78-6.60 (m, 2H), 5.08 (d, 1H), 4.93 (d, 1H), 4.68 (d, 1H), 4.49 (d, 1H); 13C NMR (75 MHz, CDCl3) δ 177.1, 163.9, 157.8, 143.6, 131.0, 128.8, 128.1, 124.7, 121.8, 120.0, 115.0, 111.6, 108.1, 99.8, 77.5, 59.2, 44.7; MS (ES+) m/z 503.4 (M+1), 505.4 (M+1).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. dissolutionThe residue was dissolved in dichloromethane (5.00 mL)
  3. stirringThe mixture was stirred at ambient temperature for one hour
  4. washThe organic layer was washed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-18d1274b2671441bb982188faeaf11b7
Source dataset
uspto-grants-2013_06
Patent number
US08466188B2

Reaction notes

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