Methyl 2-formylbenzoate → trans-3,4-Dihydro 2,2-dimethyl-4-(1-oxoisoindolin-2-yl)-6-trifluoromethylsulfonyl-2H-1-benzopyran-3-ol

HRID 1656467Notes

Reaction equation

HRID 1656467 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][CH:35]=[CH:34][C:29]=1[C:30](OC)=O)=[O:27].C(=O)([O-])O.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH3:24][C:8]1([CH3:23])[C@@H:7]([OH:25])[C@H:6]([N:5]2[CH2:30][C:29]3[C:28](=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:26]2=[O:27])[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 4

HCID 243003Methyl 2-formylbenzoateHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 15036014trans-4-amino-3,4-dihydro-2,2-dimethyl-6-trifluoromethylsulfonyl 2H-1-benzopyran-3-ol

Product 1

HCID 14748246trans-3,4-Dihydro 2,2-dimethyl-4-(1-oxoisoindolin-2-yl)-6-trifluoromethylsulfonyl-2H-1-benzopyran-3-olYield 63.2%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

A solution of 0.18 g of zinc chloride and 0.083 g of sodium cyanoborohydride in 3 ml of methanol was added to a solution of 0.40 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 0.20 g of methyl 2-formylbenzoate in 6 ml of methanol, and the resulting mixture was stirred at room temperature for 1 hour and then at 50° C. for 24 hours. At the end of this time, the mixture was cooled with ice and then mixed with a saturated aqueous solution of sodium hydrogencarbonate. The methanol was then removed by distillation under reduced pressure, and the resulting residue was diluted with water and extracted with methylene chloride. The extract was washed with water and with a saturated aqueous solution of sodium chloride, in that order, and dried over anhydrous magnesium sulfate; the solvent was then removed by distillation under reduced pressure. The resulting residue was recrystallized from ethyl acetate, to afford 0.34 g of the title compound, melting at 279°-281° C.

Workup

  1. waitat 50° C. for 24 hours
  2. temperatureAt the end of this time, the mixture was cooled with ice
  3. customThe methanol was then removed by distillation under reduced pressure
  4. additionthe resulting residue was diluted with water
  5. extractionextracted with methylene chloride
  6. washThe extract was washed with water and with a saturated aqueous solution of sodium chloride, in that order
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was then removed by distillation under reduced pressure
  9. customThe resulting residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-a7e0adba0ea8453095712f4b816b319b
Source dataset
uspto-grants-1993_10
Patent number
US05254578

Reaction notes

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