Boron tribromide → (+)-6-Fluoro-1-[(1H-indazol-4-yl)amino]-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-2,5-diol

HRID 1443135Notes

Reaction equation

HRID 1443135 reaction equation
[F:1][C:2]1[C:3]([O:29]C)=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]([NH:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]3[C:14]=1[CH:15]=[N:16][NH:17]3)[C:7]([C:23]([F:26])([F:25])[F:24])([OH:22])[CH2:6][C:5]2([CH3:28])[CH3:27].B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[F:1][C:2]1[CH:11]=[CH:10][C:9]2[CH:8]([NH:12][C:13]3[CH:21]=[CH:20][CH:19]=[C:18]4[C:14]=3[CH:15]=[N:16][NH:17]4)[C:7]([C:23]([F:25])([F:26])[F:24])([OH:22])[CH2:6][C:5]([CH3:27])([CH3:28])[C:4]=2[C:3]=1[OH:29]

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 68679948(+)-6-fluoro-5-methoxy-1-[(1H-indazol-4-yl)amino]-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-2-ol

Product 1

HCID 11165738(+)-6-Fluoro-1-[(1H-indazol-4-yl)amino]-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-2,5-diolYield 92.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

200 mg (0.472 mmol) of the above-described (−)-6-fluoro-5-methoxy-1-[(1H-indazol-4-yl)amino]-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-2-ol is mixed at room temperature with 4.7 ml of a 1 M solution of BBr3 in dichloromethane and stirred for three and three-fourths hours at room temperature. The reaction mixture is mixed drop by drop at −30° C. with saturated sodium bicarbonate solution, specifically until a pH of 8 is reached. After dilution with ethyl acetate, the cold bath is removed, and the batch is stirred vigorously for 15 minutes. After being shaken twice with ethyl acetate, the combined organic extracts are washed with water and saturated brine. After drying on sodium sulfate, and after the solvent is filtered and spun off, the residue is chromatographed on silica gel (mobile solvent:dichloromethane/methanol). 179.4 mg (92.8%) of the desired compound is obtained. The angle of rotation, measured at room temperature, is [α]D=−7.8 (c=1, MeOH).

Workup

  1. customAfter dilution with ethyl acetate, the cold bath is removed
  2. stirringthe batch is stirred vigorously for 15 minutes
  3. stirringAfter being shaken twice with ethyl acetate
  4. washthe combined organic extracts are washed with water and saturated brine
  5. customAfter drying on sodium sulfate
  6. filtrationafter the solvent is filtered
  7. customthe residue is chromatographed on silica gel (mobile solvent:dichloromethane/methanol)

Sources & evidence

ORD record
ord-0c671c762c304a1aa904db9c1bf08f9d
Source dataset
uspto-grants-2010_02
Patent number
US07659297B2

Reaction notes

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