Trichloroacetyl isocyanate → HCID 19892504, compound

HRID 893393Notes

Reaction equation

HRID 893393 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:15](=[N:23][OH:24])[CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.ClC(Cl)(Cl)[C:27]([N:29]=C=O)=[O:28].N.C(#N)C>O1CCCC1>[NH2:29][C:27]([O:24]/[N:23]=[C:15](/[C:9]1[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH:8]=1)\[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:28]

Participants

5

Reactant 3

HCID 76400Trichloroacetyl isocyanateHCID 15587892HCID 15587892, compoundHCID 73656534HCID 73656534, compound

Product 1

HCID 19892504HCID 19892504, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a magnetically-stirred solution of 1-(3-cyclopentyloxy-4-methoxyphenyl)-2-phenyl ethanone oxime (4.51 mmol, 1.48 g) in dry tetrahydrofuran (45 mL) at 0° C. is added trichloroacetyl isocyanate (5.00 mmol, 0.943 mg; 0.596 mL) dropwise over 2 minutes and the resulting solution is allowed to stir as the temperature rises slowly from 0° C. to room temperature overnight. The reaction mixture is then cooled to 0° C. and saturated NH3 /acetonitrile solution (25 mL; prepared by bubbling gaseous ammonia through CH3CN at room temperature for 1 hour) is added dropwise to the reaction mixture. The solution is allowed to stir as it warms slowly from 0° C. to room temperature. After 1.5 hours, the tetrahydrofuran is removed in vacuo and the residue is partitioned between methylene chloride (200 mL) and water (200 mL). The aqueous phase is extracted with ethyl acetate (200 mL) and the combined organics are washed with water (200 mL), dried (Na2SO4), and concentrated in vacuo to afford a mixture of product and oxime (~1:1). The residue is purified via flash chromatography (SiO2 : 1) 2% ethyl acetate/methylene chloride, 2) 5% ethyl acetate/methylene chloride, 3) 7% ethyl acetate/methylene chloride) to give a white solid which is triturated with ether/hexane and dried in vacuo at 50° C. to afford analytically-pure title compound (1.22 mmol, 0.450 g; 27%).

Workup

  1. stirringto stir as it
  2. customwarms slowly from 0° C. to room temperature
  3. waitAfter 1.5 hours
  4. customthe tetrahydrofuran is removed in vacuo
  5. customthe residue is partitioned between methylene chloride (200 mL) and water (200 mL)
  6. extractionThe aqueous phase is extracted with ethyl acetate (200 mL)
  7. washthe combined organics are washed with water (200 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford
  11. customThe residue is purified via flash chromatography (SiO2 : 1) 2% ethyl acetate/methylene chloride, 2) 5% ethyl acetate/methylene chloride, 3) 7% ethyl acetate/methylene chloride)
  12. customto give a white solid which
  13. customis triturated with ether/hexane
  14. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-51d4c9a427c44fa0bb6a0088bc809727
Source dataset
uspto-grants-1992_06
Patent number
US05124455

Reaction notes

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