Potassium Hydroxide → HCID 86701442, compound

HRID 2173906Notes

Reaction equation

HRID 2173906 reaction equation
[CH2:1]([C:4]1[C:12]([OH:13])=[CH:11][C:10]([CH3:14])=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:2]=[CH2:3].[OH-].[K+].Br[C:25](P(=O)(OCC)OCC)([F:27])[F:26]>C(#N)C.O>[CH2:1]([C:4]1[C:12]([O:13][CH:25]([F:27])[F:26])=[CH:11][C:10]([CH3:14])=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 14797Potassium Hydroxide2×HCID 144101Bromodifluoromethyl diethylphosphonateHCID 86701440HCID 86701440, compound

Product 1

HCID 86701442HCID 86701442, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-Butyl 4-allyl-5-hydroxy-7-methyl-1H-indole-1-carboxylate (3.6 g, 12.53 mmol) was dissolved in acetonitrile (62.6 mL) and water (62.6 mL), then KOH (14.06 g, 251 mmol) was added and the solution was stirred until all the KOH went into solution. The resulting solution was then cooled to −78° C. (solution froze) and diethyl bromodifluoromethylphosphonate (4.45 mL, 25.06 mmol) was added. The reaction was removed from the dry ice bath and allowed to warm to room temperature. After 1 hour, EtOAc and water were added, and the resulting layers were separated. The aqueous layer was further extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-40% EtOAc in heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.69 (d, J=3.79 Hz, 1H) 7.08 (t, J=74.7 Hz, 1H) 6.96 (s, 1H) 6.76 (d, J=3.79 Hz, 1H) 5.89 (dd, J=16.93, 10.36 Hz, 1H) 4.91-5.05 (m, 2H) 3.57 (d, J=6.32 Hz, 2H) 1.59 (s, 9H). MS (ESI+) m/z 338.1 (M+H).

Workup

  1. additionwas added
  2. customThe reaction was removed from the dry ice bath
  3. additionEtOAc and water were added
  4. customthe resulting layers were separated
  5. extractionThe aqueous layer was further extracted with EtOAc
  6. washThe combined organics were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash chromatography (0-40% EtOAc in heptanes)

Sources & evidence

ORD record
ord-442cba1a61f749a3a30d21a41b0bd46d
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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