Phenylboronic Acid → 1,1,1-Trifluoro-4-(4-methoxybiphenyl-3-yl)4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-ol

HRID 400674Notes

Reaction equation

HRID 400674 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:28][CH3:29])=[C:6]([C:8]([CH3:27])([CH3:26])[CH2:9][C:10]([CH2:16][C:17]2[NH:25][C:20]3=[CH:21][N:22]=[CH:23][CH:24]=[C:19]3[CH:18]=2)([OH:15])[C:11]([F:14])([F:13])[F:12])[CH:7]=1.[F-].[K+].[C:32]1(B(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1COCC1.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:12][C:11]([F:14])([F:13])[C:10]([CH2:16][C:17]1[NH:25][C:20]2=[CH:21][N:22]=[CH:23][CH:24]=[C:19]2[CH:18]=1)([OH:15])[CH2:9][C:8]([C:6]1[CH:7]=[C:2]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:3]=[CH:4][C:5]=1[O:28][CH3:29])([CH3:27])[CH3:26]

Participants

7

Reactant 3

HCID 66827Phenylboronic AcidHCID 522689Potassium FluorideHCID 469390184-(5-bromo-2-methoxyphenyl)-1,1,1-trifluoro-4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-ol

Product 1

HCID 469390191,1,1-Trifluoro-4-(4-methoxybiphenyl-3-yl)4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-olYield 40%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-(5-bromo-2-methoxyphenyl)-1,1,1-trifluoro-4-methyl-2-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-ol (188 mg, 0.4 mmol), Pd(OAc)2 (9 mg, 0.04 mmol), DCyBPP ((2-dicyclohexylphosphino)biphenyl, 28 mg, 0.08 mmol), and KF (93 mg, 1.6 mmol) in 3 mL of THF at room temperature was treated with phenylboronic acid (74 mg, 0.6 mmol). The reaction mixture was microwaved for 20 minutes at 120° C., cooled to room temperature, diluted with 20 mL of ethyl acetate and filtered through diatomaceous earth. The filtrate was washed with 5 mL of 1.0 M aqueous sodium hydroxide solution, water, and 5 mL of brine. The organic phase was dried over magnesium sulfate, filtered, and the solvent evaporated in vacuo. The residue was purified silica gel chromatography to provide 75 mg (40% yield) of the title compound as a white solid.

Workup

  1. customThe reaction mixture was microwaved for 20 minutes at 120° C.
  2. filtrationfiltered through diatomaceous earth
  3. washThe filtrate was washed with 5 mL of 1.0 M aqueous sodium hydroxide solution, water, and 5 mL of brine
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customThe residue was purified silica gel chromatography

Sources & evidence

ORD record
ord-258ee877ac684ea9800514fd4cf18580
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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