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

HRID 1656458Notes

Reaction equation

HRID 1656458 reaction equation
C([BH3-])#N.[Na+].[NH2:5][C@@H:6]1[C:11]2[CH:12]=[C:13]([S:16]([C:19]([F:22])([F:21])[F:20])(=[O:18])=[O:17])[CH:14]=[CH:15][C:10]=2[O:9][C:8]([CH3:24])([CH3:23])[C@H:7]1[OH:25].[CH:26]([C:28]1[CH:37]=[CH:36][C:35]([N+:38]([O-:40])=[O:39])=[CH:34][C:29]=1[C:30](OC)=[O:31])=O>C(O)CC.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH3:24][C:8]1([CH3:23])[C@@H:7]([OH:25])[C@H:6]([N:5]2[CH2:26][C:28]3[C:29](=[CH:34][C:35]([N+:38]([O-:40])=[O:39])=[CH:36][CH:37]=3)[C:30]2=[O:31])[C:11]2[CH:12]=[C:13]([S:16]([C:19]([F:21])([F:22])[F:20])(=[O:18])=[O:17])[CH:14]=[CH:15][C:10]=2[O:9]1

Participants

7

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 15036014trans-4-amino-3,4-dihydro-2,2-dimethyl-6-trifluoromethylsulfonyl 2H-1-benzopyran-3-olHCID 19788121Methyl 2-formyl-5-nitrobenzoate

Product 1

HCID 67859046trans-3,4-Dihydro-2,2-dimethyl-4-(6-nitro 1-oxoisoindolin-2-yl)-6-trifluoromethylsulfonyl-2H-1-benzopyran-3-olYield 87%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 10311-PropanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 0.164 g of zinc chloride and 0.075 g of sodium cyanoborohydride in 3.3 ml of propanol was added to a solution of 0.326 g of trans-4-amino-3,4-dihydro-2,2-dimethyl-6-trifluoromethylsulfonyl 2H-1-benzopyran-3-ol (prepared from its hydrochloride prepared as described in Preparation 9) and 0.224 g of methyl 2-formyl-5-nitrobenzoate in 3.3 ml of propanol, and the resulting mixture was heated under reflux in an oil bath kept at 140° C. for 1.5 hours. At the end of this time, the reaction mixture was diluted with 150 ml of ethyl acetate, and the resulting solution was washed with 1N aqueous hydrochloric acid, with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order. The mixture was then dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was recrystallized from a mixture of ethyl acetate and hexane to give 0.424 g of the title compound, melting at 264°-266° C.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux in an oil bath
  3. washthe resulting solution was washed with 1N aqueous hydrochloric acid, with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  4. dry with materialThe mixture was then dried over anhydrous sodium sulfate
  5. customafter which the solvent was removed by distillation under reduced pressure
  6. customThe resulting residue was recrystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-4e84ecbecc8b44cd98cbb13fe786bb65
Source dataset
uspto-grants-1993_10
Patent number
US05254578

Reaction notes

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