Hydrochloric Acid → 6-Chlorochroman-3-one

HRID 1803752Notes

Reaction equation

HRID 1803752 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][C:6](C(O)=O)=[CH:5]2.C(N(CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:29])C=CC=CC=1.Cl>ClCCl.C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][C:6](=[O:29])[CH2:5]2

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 5969296-chloro-2H-chromene-3-carboxylic acid

Product 1

HCID 218196376-Chlorochroman-3-one

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloro-2H-chromene-3-carboxylic acid (Avocado, 4.90 g, 23.3 mmol) in dichloromethane (50 mL) was added triethylamine (4 mL) and diphenylphosphoryl azide (7.04 g, 25.6 mmol) in toluene (20 mL). The flask was equipped with a Dean-Stark trap, and the mixture was heated to reflux. After 1.5 hours, toluene (50 mL) was added and the mixture continued to reflux for 2.5 hours and was then cooled to ambient temperature. Hydrochloric acid (6N, 40 mL) was added, and the biphasic mixture was heated at reflux for 3.5 hours then cooled to ambient temperature. Ethyl acetate (200 mL) and water (200 mL) were added and the separated organic layer was washed sequentially with saturated sodium bicarbonate (2×200 mL) followed by brine. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrate under reduced pressure, and chromatographed on silica gel eluting with 10-to-60% dichloromethane in hexane to afford the title compound. MS (DCI) m/z 181.97 (M+H)+.

Workup

  1. customThe flask was equipped with a Dean-Stark trap
  2. temperaturethe mixture was heated to reflux
  3. temperatureto reflux for 2.5 hours
  4. temperaturethe biphasic mixture was heated
  5. temperatureat reflux for 3.5 hours
  6. temperaturethen cooled to ambient temperature
  7. washthe separated organic layer was washed sequentially with saturated sodium bicarbonate (2×200 mL)
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrate under reduced pressure
  11. customchromatographed on silica gel eluting with 10-to-60% dichloromethane in hexane

Sources & evidence

ORD record
ord-776125f79fa5400b8e840a5231f624b2
Source dataset
uspto-grants-2013_01
Patent number
US08350083B2

Reaction notes

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