2,6-Lutidine → 2-{1-[2-(tert-butyldimethylsilanyloxy)-2-methyl-propyl]-1H-indazol-5-yloxy}-5-fluorobenzonitrile

HRID 909240Notes

Reaction equation

HRID 909240 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][C:21]([OH:24])([CH3:23])[CH3:22])[N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8].N1C(C)=CC=CC=1C.[Si:33](OS(C(F)(F)F)(=O)=O)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>ClCCl.CCOCC>[Si:33]([O:24][C:21]([CH3:22])([CH3:23])[CH2:20][N:16]1[C:17]2[C:13](=[CH:12][C:11]([O:10][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:9][C:6]=3[C:7]#[N:8])=[CH:19][CH:18]=2)[CH:14]=[N:15]1)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]

Participants

6

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 674118315-Fluoro-2-[1-(2-hydroxy-2-methylpropyl)-1H-indazol-5-yloxy]-benzonitrile

Product 1

HCID 674118002-{1-[2-(tert-butyldimethylsilanyloxy)-2-methyl-propyl]-1H-indazol-5-yloxy}-5-fluorobenzonitrileYield 94%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a cooled (0° C.) solution of 5-Fluoro-2-[1-(2-hydroxy-2-methylpropyl)-1H-indazol-5-yloxy]-benzonitrile (0.070 g, 0.215 mmol) and 2,6-lutidine (0.030 g, 0.284 mmol) in dichloromethane (2 mL) was added TBSOTf (0.063 g, 0.240 mmol). The reaction mixture was warmed to room temperature and stirred for 1 hour. The mixture was diluted with ether (50 mL) and washed with 0.2N HCl, NaHCO3, and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was chromatographed eluting with ether/hexanes (1:3) to afford 0.071 g of pale yellow oil (94% yield).

Workup

  1. washwashed with 0.2N HCl, NaHCO3, and brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was chromatographed
  5. washeluting with ether/hexanes (1:3)

Sources & evidence

ORD record
ord-3ea3b86d10f34a4daffd260c30fe9737
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

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