Trichloroethanol → HCID 19819812, compound

HRID 1031145Notes

Reaction equation

HRID 1031145 reaction equation
[CH3:1][C:2]([C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C(O)=O.C([N:20](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[Cl:42]C(Cl)(Cl)CO>C1COCC1.[Zn].C(O)(=O)C.O>[ClH:42].[CH3:1][C:2]([C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)([NH2:20])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

9

Reactant 4

HCID 8259TrichloroethanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 19819809HCID 19819809, compound

Product 1

HCID 19819812HCID 19819812, compound

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

The acid from step (a) (25 g, 0.102 mol) was dissolved in THF(390 mL) and triethylamine (14.1 mL) was added. Diphenylphosphoryl azide (23.4 mL) was added and the mixture was heated at 65° C. for 5 hours. The reaction was cooled to room temperature and 2,2,2-trichloroethanol (46.1 mL) was added portionwise and then the reaction was heated to reflux for 40 hours. The reaction was cooled to 0° C. and water (40 mL), glacial acetic acid (360 mL) and zinc dust (132 g) were added. The ice bath was removed and the reaction was stirred overnight. After filtration of the reaction mixture through a bed of celite the filtrate was concentrated and the residue was dissolved in ethyl acetate (800 mL). The ethyl acetate was washed with 1N.NaOH (800 mL) and water (800 ml). The ethyl acetate layer was separated, dried (MgSO4) and concentrated to dryness. The residual oil was converted to the hydrochloride salt with ethanolic hydrogen chloride and precipitated by the addition of diethyl ether. A 1 g portion of the hydrochloride was recrystallized from ethyl acetate(20 mL)/MeOH(5 mL)/hexanes(15 mL) to give the title compound (0.8 g), mp 205°-206° C.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 40 hours
  4. temperatureThe reaction was cooled to 0° C.
  5. customThe ice bath was removed
  6. filtrationAfter filtration of the reaction mixture through a bed of celite the filtrate
  7. concentrationwas concentrated
  8. dissolutionthe residue was dissolved in ethyl acetate (800 mL)
  9. washThe ethyl acetate was washed with 1N
  10. customThe ethyl acetate layer was separated
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated to dryness
  13. customprecipitated by the addition of diethyl ether
  14. customA 1 g portion of the hydrochloride was recrystallized from ethyl acetate(20 mL)/MeOH(5 mL)/hexanes(15 mL)

Sources & evidence

ORD record
ord-894dc6bdc31a422f8a9152f36f540f20
Source dataset
uspto-grants-1992_04
Patent number
US05109017

Reaction notes

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