Potassium Fluoride → HCID 11543746, compound

HRID 2250519Notes

Reaction equation

HRID 2250519 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[NH:7][C:6](=[O:12])[C:5]2([CH3:14])[CH3:13].[CH3:15][N:16]1[C:20]([C:21]#[N:22])=[CH:19][CH:18]=[C:17]1B(O)O.[F-].[K+]>>[F:11][C:9]1[CH:10]=[C:2]([C:17]2[N:16]([CH3:15])[C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[CH:3]=[C:4]2[C:8]=1[NH:7][C:6](=[O:12])[C:5]2([CH3:14])[CH3:13]

Participants

4

Reactant 3

HCID 522689Potassium FluorideHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acidHCID 119764375-Bromo-7-fluoro-3,3-dimethyl-1,3-dihydro-2H-indol-2-one

Product 1

HCID 11543746HCID 11543746, compoundYield 80%

Conditions

Temperature
25 °C

Procedure

5-Bromo-7-fluoro-3,3-dimethyl-1,3-dihydro-indol-2-one (5.16 g, 20.0 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (5.4 g, 36 mmol), KF (3.83 g, 66 mmol), and Pd2(dba)3 monochloroform adduct (516 mg, 0.500 mmol) were added to a 200 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 min. THF (50 mL) was added and the mixture was purged with nitrogen for an additional 5 min. A solution of tri-t-butylphosphine (10% wt in hexanes) (2.97 mL, 1.00 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 5 h. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed through with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification by flash chromatography (20% acetone/hexane) afforded the title compound (4.5 g, 80%) as an off-white solid.

Workup

  1. customThe flask was sealed
  2. custompurged with nitrogen for 5 min
  3. additionTHF (50 mL) was added
  4. customthe mixture was purged with nitrogen for an additional 5 min
  5. additionA solution of tri-t-butylphosphine (10% wt in hexanes) (2.97 mL, 1.00 mmol) was added via syringe
  6. additionThe mixture was diluted with 250 mL of EtOAc
  7. filtrationfiltered through a plug of silica gel
  8. washwashed through with 200 mL of EtOAc
  9. concentrationconcentrated
  10. customto give a crude brown/black semi-solid
  11. customPurification by flash chromatography (20% acetone/hexane)

Sources & evidence

ORD record
ord-7cd84258560949bd9dbc6321b21ff0cb
Source dataset
uspto-grants-2008_01
Patent number
US07317037B2

Reaction notes

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