Phosphorus trichloride → HCID 136340685, compound

HRID 1777196Notes

Reaction equation

HRID 1777196 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]2[C:13]1[CH:22]=[CH:21][C:20]2[CH2:19][CH2:18][CH2:17][CH:16]([OH:23])[C:15]=2[N+:14]=1[O-])#[N:2].P(Cl)(Cl)Cl>C(OCC)(=O)C.C(#N)C>[OH:12][C:7]1[NH:8][C:9]2[C:5]([C:6]=1[C:13]1[CH:22]=[CH:21][C:20]3[CH2:19][CH2:18][CH2:17][CH:16]([OH:23])[C:15]=3[N:14]=1)=[CH:4][C:3]([C:1]#[N:2])=[CH:11][CH:10]=2

Participants

5

Reactant 2

HCID 24387Phosphorus trichlorideHCID 66823338HCID 66823338, compound

Product 1

HCID 136340685HCID 136340685, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

To a suspension of crude 2-(5-cyano-2-oxoindolin-3-yl)-8-hydroxy-5,6,7,8-tetrahydroquinoline 1-oxide (263 mg, 0.819 mmol) in ethyl acetate (12 mL) and acetonitrile (12 mL) was added dropwise a solution of phosphorous trichloride (0.644 mL, 7.37 mmol) in ethyl acetate (4 mL). The resulting suspension was stirred at RT. After 24 h the mixture was diluted with ethyl acetate and washed with a saturated sodium bicarbonate solution (2×). The aqueous phase was re-extracted with ethyl acetate (1×) and the combined organic extracts were dried over sodium sulfate, filtered, and evaporated to dryness (52 mg). The crude was dissolved in a mixture of water (2 mL) and dimethylformamide (3 mL) and the solution was heated in a microwave oven at 120° C. for 5 min. After cooling to RT the reaction mixture was diluted with ethyl acetate was washed with brine (5×). The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness. The crude was purified by flash chromatography (silica gel, dichloromethane/methanol) yielding yellow solid. Amount 8.6 mg. Yield 18%.

Workup

  1. washwashed with a saturated sodium bicarbonate solution (2×)
  2. extractionThe aqueous phase was re-extracted with ethyl acetate (1×)
  3. dry with materialthe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness (52 mg)
  6. dissolutionThe crude was dissolved in a mixture of water (2 mL) and dimethylformamide (3 mL)
  7. temperaturethe solution was heated in a microwave oven at 120° C. for 5 min
  8. temperatureAfter cooling to RT the reaction mixture
  9. additionwas diluted with ethyl acetate
  10. washwas washed with brine (5×)
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. filtrationfiltered
  13. customevaporated to dryness
  14. customThe crude was purified by flash chromatography (silica gel, dichloromethane/methanol)
  15. customyielding yellow solid

Sources & evidence

ORD record
ord-0cea1e3529ac4e9e9ebb080b64fc00c6
Source dataset
uspto-grants-2016_02
Patent number
US09266855B2

Reaction notes

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