Boron tribromide → HCID 86599915, compound

HRID 1444389Notes

Reaction equation

HRID 1444389 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:30]C)=[C:6]([C:8]([CH3:29])([CH3:28])[CH2:9][C:10]([OH:27])([C:23]([F:26])([F:25])[F:24])[CH:11]=[N:12][C:13]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:14]=2[CH2:15][NH:16][C:17]3=[O:22])[CH:7]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:30])=[C:6]2[C:7]=1[CH:11]([NH:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]3[C:14]=1[CH2:15][NH:16][C:17]3=[O:22])[C:10]([OH:27])([C:23]([F:26])([F:25])[F:24])[CH2:9][C:8]2([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 17985033HCID 17985033, compound

Product 1

HCID 86599915HCID 86599915, compoundYield 7.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

420 mg (0.958 mmol) of the compound 4-{[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentylidene]amino}2,3-dihydroisoindol-1-one that is described in the paragraph above is mixed with 9.6 ml of a 1 M solution of boron tribromide in dichloromethane, and it is stirred for 1¾ hours at room temperature. The reaction mixture is mixed drop by drop with saturated sodium bicarbonate at −30° C., specifically up to pH 8. After dilution with ethyl acetate, the cold bath is removed and stirred vigorously for 15 minutes. After 2× extraction with ethyl acetate, the organic phases are washed with water and saturated sodium chloride solution. After the solvent is dried (sodium sulfate) and spun off, the residue is chromatographed on a Flashmaster (silica gel, NH2 phase) (mobile solvent dichloromethane/methanol). 67.7 mg (16.6%) of 4-{[8-fluoro-2-hydroxy-5-methoxy-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino}-2,3-dihydroisoindol-1-one (diastereomer A, F1); 12.9 mg (3.2%) of 4-{[8-fluoro-2,5 dihydroxy-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino}-2,3-dihydroisoindol-1-one (diastereomer A, F2), and 32.2 mg (7.9%) of 4-{[8-fluoro-2,5-dihydroxy-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino}-2,3-dihydroisoindol-1-one (diastereomer B, F3) are isolated.

Workup

  1. customAfter dilution with ethyl acetate, the cold bath is removed
  2. stirringstirred vigorously for 15 minutes
  3. extractionAfter 2× extraction with ethyl acetate
  4. washthe organic phases are washed with water and saturated sodium chloride solution
  5. dry with materialAfter the solvent is dried (sodium sulfate)
  6. customthe residue is chromatographed on a Flashmaster (silica gel, NH2 phase) (mobile solvent dichloromethane/methanol)

Sources & evidence

ORD record
ord-b87e6ecb010244e6803dc87a35cca367
Source dataset
uspto-grants-2010_02
Patent number
US07662821B2

Reaction notes

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