Ethyl Acetate → (rac.) 5-{[7-Chloro-6-fluoro-2,5-dihydroxy-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino}-isoquinolin-1-one

HRID 1443304Notes

Reaction equation

HRID 1443304 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:30])([CH3:29])[CH2:9][C:10]([OH:28])([C:24]([F:27])([F:26])[F:25])[CH:11]=[N:12][C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH:15]=[CH:16][NH:17][C:18]3=[O:23])=[C:4]([O:31]C)[C:3]=1[F:33].B(Br)(Br)Br.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]2[C:5]([C:8]([CH3:29])([CH3:30])[CH2:9][C:10]([OH:28])([C:24]([F:27])([F:25])[F:26])[CH:11]2[NH:12][C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH:15]=[CH:16][NH:17][C:18]3=[O:23])=[C:4]([OH:31])[C:3]=1[F:33]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 17989293(Rac.) 5-{[4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentylidene]amino}isoquinolin-1(2h)-one

Product 1

HCID 86600872(rac.) 5-{[7-Chloro-6-fluoro-2,5-dihydroxy-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino}-isoquinolin-1-oneYield 31.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

80.3 mg (0.166 mmol) of (rac.) 5-{[4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentylidene]amino}isoquinolin-1(2H)-one is mixed at room temperature with 1.7 ml of a 1 molar solution of boron tribromide in dichloromethane, and it is stirred for two and one-half hours at room temperature. The reaction mixture is mixed with ice, and then saturated sodium bicarbonate solution is added in drops (pH 8). After ethyl acetate is added, and after ten minutes of vigorous stirring at room temperature, the aqueous phase is extracted twice with ethyl acetate. The combined organic phases are washed with water and with brine, dried, and after the solvent is spun off, the residue is chromatographed on a Flashmaster. 24.6 mg (31.6%) of the desired compound is isolated.

Workup

  1. additionThe reaction mixture is mixed with ice
  2. stirringafter ten minutes of vigorous stirring at room temperature
  3. extractionthe aqueous phase is extracted twice with ethyl acetate
  4. washThe combined organic phases are washed with water and with brine
  5. customdried
  6. customthe residue is chromatographed on a Flashmaster

Sources & evidence

ORD record
ord-8a7be34f8a9741829910930c74460cbb
Source dataset
uspto-grants-2010_02
Patent number
US07659297B2

Reaction notes

Loading…