Boron tribromide → HCID 86600871, compound

HRID 420633Notes

Reaction equation

HRID 420633 reaction equation
[Cl:1][C:2]1[C:3]([O:33]C)=[C:4]2[C:9](=[CH:10][C:11]=1[CH3:12])[CH:8]([NH:13][C:14]1[CH:23]=[CH:22][C:21]([F:24])=[C:20]3[C:15]=1[CH:16]=[N:17][C:18]([CH3:25])=[N:19]3)[C:7]([C:27]([F:30])([F:29])[F:28])([OH:26])[CH2:6][C:5]2([CH3:32])[CH3:31].B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)(=O)C>[Cl:1][C:2]1[C:11]([CH3:12])=[CH:10][C:9]2[CH:8]([NH:13][C:14]3[CH:23]=[CH:22][C:21]([F:24])=[C:20]4[C:15]=3[CH:16]=[N:17][C:18]([CH3:25])=[N:19]4)[C:7]([C:27]([F:28])([F:29])[F:30])([OH:26])[CH2:6][C:5]([CH3:31])([CH3:32])[C:4]=2[C:3]=1[OH:33]

Participants

6

Reactant 3

HCID 25134Boron tribromide2×HCID 516892Sodium BicarbonateHCID 66657294HCID 66657294, compound

Product 1

HCID 86600871HCID 86600871, compoundYield 98.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

40 mg (0.08 mmol) of (rac.) 6-chloro-1-[(8-fluoro-2-methylquinazolin-5-yl)-amino]-5-methoxy-4,4,7-trimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-2-ol is mixed at room temperature with 0.8 ml of a 1 molar solution of boron tribromide in dichloromethane, and it is stirred for four hours at room temperature. Since no reaction was carried out, another 0.8 ml of the boron tribromide solution was added. After 16 hours of stirring at room temperature, the reaction was complete. At −30° C., saturated sodium bicarbonate solution is now carefully added in drops, and the batch is diluted with ethyl acetate. After the cold bath is removed, it is stirred vigorously at room temperature for 10 minutes. The batch is extracted twice with ethyl acetate. The combined organic phases are washed with water and with brine, dried, and the residue is chromatographed on silica gel (mobile solvent methanol/dichloromethane) after the solvent is spun off. 38.2 mg (98.4%) of the desired compound is isolated.

Workup

  1. stirringAfter 16 hours of stirring at room temperature
  2. customAfter the cold bath is removed
  3. stirringit is stirred vigorously at room temperature for 10 minutes
  4. extractionThe batch is extracted twice with ethyl acetate
  5. washThe combined organic phases are washed with water and with brine
  6. customdried
  7. customthe residue is chromatographed on silica gel (mobile solvent methanol/dichloromethane) after the solvent

Sources & evidence

ORD record
ord-189aa82a58a54a8984943f05bcd6e86e
Source dataset
uspto-grants-2012_01
Patent number
US08097627B2

Reaction notes

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