Diethyl Ether → HCID 67417764, compound

HRID 912470Notes

Reaction equation

HRID 912470 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][C:12]([CH3:15])(O)[CH3:13])=[CH:4][C:3]=1[O:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[F:24].NC(N)CS(F)(F)[F:29].[OH-].[K+].C(OCC)C>C(Cl)Cl>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][C:12]([F:29])([CH3:15])[CH3:13])=[CH:4][C:3]=1[O:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[F:24]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 14797Potassium HydroxideHCID 674164781-(6-bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)-2-methylpropan-2-olHCID 86631053HCID 86631053, compound

Product 1

HCID 67417764HCID 67417764, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(6-Bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)-2-methylpropan-2-ol (19.8 g, 49.8 mmol) in DCM (150 mL) was cooled with a dry-ice acetone bath to −73° C. (Diaminoethyl)sulfur trifluoride (6.9 mL, 52.3 mmol) was added dropwise over 2 min; the temperature rose to −62° C. The resulting solution was stirred in the bath for a further 1 hr, then at ambient temperature for 1 hour. The reaction mixture was poured into a separatory funnel containing cold 10% KOH (250 mL), and then diethyl ether (500 mL) was added. After shaking, the organic layer was washed with brine (150 mL), dried over sodium sulfate and evaporated. The residue was chromatographed on silica gel using 85/15 hexanes/EtOAc as eluent. Fractions containing product were pooled and the solvent removed under reduced pressure to afford the title compound as an orange oil (13.4 g, 78%).

Workup

  1. additionwas added dropwise over 2 min
  2. customrose to −62° C
  3. waitat ambient temperature for 1 hour
  4. additionThe reaction mixture was poured into a separatory funnel
  5. stirringAfter shaking
  6. washthe organic layer was washed with brine (150 mL)
  7. dry with materialdried over sodium sulfate
  8. customevaporated
  9. customThe residue was chromatographed on silica gel using 85/15 hexanes/EtOAc as eluent
  10. additionFractions containing product
  11. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-a43a133e445343b4a29d62e794ed0f52
Source dataset
uspto-grants-2011_09
Patent number
US08026233B2

Reaction notes

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