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

HRID 1869318Notes

Reaction equation

HRID 1869318 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-quarters 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 2× shaking 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 2× shaking 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-c613773d4c4248a284dff75bbc020f1c
Source dataset
uspto-grants-2009_12
Patent number
US07638515B2

Reaction notes

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