Hydrochloric Acid → trans-3,4-Dihydro-2,2 dimethyl-4-(4-nitro-1-oxoisoindolin-2-yl)-6-trifluoromethylsulfonyl-2H-1-benzopyran-3-ol

HRID 1656460Notes

Reaction equation

HRID 1656460 reaction equation
[NH2:1][C@@H:2]1[C:7]2[CH:8]=[C:9]([S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH3:20])([CH3:19])[C@H:3]1[OH:21].C(N(CC)CC)C.Br[CH2:30][C:31]1[C:41]([N+:42]([O-:44])=[O:43])=[CH:40][CH:39]=[CH:38][C:32]=1[C:33](OCC)=[O:34].Cl>CN(C)C=O>[CH3:20][C:4]1([CH3:19])[C@@H:3]([OH:21])[C@H:2]([N:1]2[CH2:30][C:31]3[C:32](=[CH:38][CH:39]=[CH:40][C:41]=3[N+:42]([O-:44])=[O:43])[C:33]2=[O:34])[C:7]2[CH:8]=[C:9]([S:12]([C:15]([F:17])([F:18])[F:16])(=[O:14])=[O:13])[CH:10]=[CH:11][C:6]=2[O:5]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 15036014trans-4-amino-3,4-dihydro-2,2-dimethyl-6-trifluoromethylsulfonyl 2H-1-benzopyran-3-olHCID 19788106Ethyl 2-(bromomethyl)-3-nitrobenzoate

Product 1

HCID 67858972trans-3,4-Dihydro-2,2 dimethyl-4-(4-nitro-1-oxoisoindolin-2-yl)-6-trifluoromethylsulfonyl-2H-1-benzopyran-3-olYield 54.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

0.362 g of trans-4 amino-3,4-dihydro-2,2-dimethyl-6-trifluoromethylsulfonyl-2H-1-benzopyran-3-ol (prepared from its hydrochloride, in turn prepared as described in Preparation 9) and 0.30 ml of triethylamine were added to a solution of 0.367 g of ethyl 2-bromomethyl-3-nitrobenzoate in 7.4 ml of dimethylformamide, and the resulting mixture was stirred at 100° C. for 1 hour in an atmosphere of nitrogen. The reaction mixture was then stirred under reflux of the solvent (at 152° C.) for a further 1 hour, after which the mixture was poured into dilute aqueous hydrochloric acid and extracted with ethyl acetate. The extract was then washed with water, with a saturated aqueous solution of sodium hydrogencarbonate and a with saturated aqueous solution of sodium chloride, after which it was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure, and the residue was purified by column chromatography through silica gel, using a 1:1:1 by volume mixture of ethyl acetate, cyclohexane and tetrahydrofuran as the eluent. The product obtained from the eluate was recrystallized from a mixture of tetrahydrofuran and hexane to give 0.295 g of the title compound, melting at 292°-295° C.

Workup

  1. stirringThe reaction mixture was then stirred
  2. temperatureunder reflux of the solvent (at 152° C.) for a further 1 hour
  3. extractionextracted with ethyl acetate
  4. washThe extract was then washed with water, with a saturated aqueous solution of sodium hydrogencarbonate
  5. dry with materiala with saturated aqueous solution of sodium chloride, after which it was dried over anhydrous sodium sulfate
  6. customThe solvent was then removed by distillation under reduced pressure
  7. customthe residue was purified by column chromatography through silica gel
  8. additionby volume mixture of ethyl acetate, cyclohexane and tetrahydrofuran as the eluent
  9. customThe product obtained from the eluate
  10. customwas recrystallized from a mixture of tetrahydrofuran and hexane

Sources & evidence

ORD record
ord-e9d34b430ccc49789d12a56775cac595
Source dataset
uspto-grants-1993_10
Patent number
US05254578

Reaction notes

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