Hydrochloric Acid → HCID 21265745, compound

HRID 1378556Notes

Reaction equation

HRID 1378556 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8](=[CH:12][C:13]2[CH:18]=[CH:17][C:16]([S:19][CH3:20])=[CH:15][CH:14]=2)C(O)=O)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:35])C=CC=CC=1.C(O)(C)(C)C.Cl>C1(C)C=CC=CC=1.O>[F:1][C:2]1[CH:3]=[C:4]([C:8](=[O:35])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([S:19][CH3:20])=[CH:15][CH:14]=2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 54085736HCID 54085736, compound

Product 1

HCID 21265745HCID 21265745, compoundYield 40.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the intermediate from Step 1 (3.57 g, 12.4 mmol) and triethylamine (1.41 g, 13.9 mmol) dissolved in 35 mL of anhydrous toluene was cooled to 0° C. and treated with diphenylphosphoryl azide (3.53 g, 12.8 mmol). The solution was maintained at 0° C. for twenty minutes and warmed to room temperature for 3 hours. The reaction was poured into water, extracted with ether, dried over magnesium sulfate, and concentrated in vacuo to remove the ether. The remaining toluene solution was heated to reflux for 1 hour. tert-Butyl alcohol (4 mL, 42 mmol) was added to the reaction mixture. After an additional twenty minutes, concentrated hydrochloric acid (4 mL) was cautiously added and the reaction maintained at 80° C. overnight (14 hours). After cooling the solution to room temperature, the mixture was poured into a separatory funnel and washed with water. The toluene layer was dried with anhydrous MgSO4, filtered and concentrated in vacuo to give a yellow powder. The crude solid was crystallized from a mixture of dichloromethane and isooctane to provide 1.30 g (40%) of the desired ketone: mp 116°-120° C. 1H NMR (CDCl3) 300 MHz 7.77 (d, J=7.9 Hz, 1H), 7.68 (dt, J=9.4 Hz 2.6 Hz, 1H), 7.43 (m, 1H), 7.21-7.29 (m, 3H), 7.18 (d, J=8.3 Hz, 2H), 4.22 (s, 2H), 2.46 (s, 3H); 19F NMR (CDCl3) -111.82 (m). Mass spectrum M+H=261.

Workup

  1. temperatureThe solution was maintained at 0° C. for twenty minutes
  2. temperaturewarmed to room temperature for 3 hours
  3. extractionextracted with ether
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto remove the ether
  7. temperatureThe remaining toluene solution was heated
  8. temperatureto reflux for 1 hour
  9. waitAfter an additional twenty minutes
  10. temperaturethe reaction maintained at 80° C. overnight (14 hours)
  11. temperatureAfter cooling the solution to room temperature
  12. additionthe mixture was poured into a separatory funnel
  13. washwashed with water
  14. dry with materialThe toluene layer was dried with anhydrous MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customto give a yellow powder
  18. customThe crude solid was crystallized from a mixture of dichloromethane and isooctane

Sources & evidence

ORD record
ord-6497c3327c5747fa858df37afcddcc70
Source dataset
uspto-grants-1997_09
Patent number
US05668161

Reaction notes

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