Triphosgene → HCID 178522047, compound

HRID 1023890Notes

Reaction equation

HRID 1023890 reaction equation
C([N:20]1[CH:24]=[C:23]([C:25]2[CH:40]=[CH:39][CH:38]=[CH:37][C:26]=2[O:27][CH2:28][CH2:29][C:30]2[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=2)[N:22]=[CH:21]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.Cl[C:42](Cl)([O:44]C(=O)OC(Cl)(Cl)Cl)Cl.[O:53]1[CH2:58][CH2:57][CH:56]([NH2:59])[CH2:55][CH2:54]1.C(=O)(O)[O-].[Na+]>ClCCl.C(N(CC)CC)C>[NH:20]1[CH:24]=[C:23]([C:25]2[CH:40]=[CH:39][CH:38]=[CH:37][C:26]=2[O:27][CH2:28][CH2:29][C:30]2[CH:31]=[CH:32][C:33]([NH:34][C:42]([NH:59][CH:56]3[CH2:57][CH2:58][O:53][CH2:54][CH2:55]3)=[O:44])=[CH:35][CH:36]=2)[N:22]=[CH:21]1

Participants

7

Reactant 4

HCID 94429TriphosgeneHCID 4192234-AminotetrahydropyranHCID 516892Sodium BicarbonateHCID 672072114-(2-(2-(1-Trityl-1H-imidazol-4-yl)phenoxy)ethyl)aniline

Product 1

HCID 178522047HCID 178522047, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

4-(2-(2-(1-trityl-1H-imidazol-4-yl)phenoxy)ethyl)aniline (50.0 mg. 0.096 mmol) was dissolved in dichloromethane (DCM, 5 ml) and triethylamine (1 ml), and a solution of triphosgene (0.105 mmol) in DCM (5 ml) was then added to the solution at 0° C. The mixture was stirred at room temperature under N2 for 2 h. Next, tetrahydro-2H-pyran-4-amine (20.0 mg, 0.192 mmol) was added to the reaction solution, and the mixture was stirred at room temperature under N2 for overnight. A saturated aqueous sodium bicarbonate solution was added to the reaction solution, followed by extraction with DCM (3×15 ml). The DCM layer was dried over Na2SO4. The solvent was removed by distillation under the reduced pressure. The residue was dissolved in MeOH/AcOH (4:1, 4 mL) and heated at 80° C. for 2 h. The reaction mixture was basified with aqueous 10% NaOH and the aqueous layer extracted with ethyl acetate (2×30 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography. Yield=78%. 1H NMR (MeOH-d4): 1.40-1.54 (m, 2H), 1.81-1.92 (m, 2H), 3.11-3.15 (m, 2H), 3.46-3.53 (m, 2H), 3.55-3.80 (m, 1H), 3.85-3.95 (m, 2H), 4.35 (t, 2H, J=6.6 Hz), 6.95-7.00 (m, 1H), 7.05-7.13 (m, 2H), 7.19-7.30 (m, 5H), 7.70 (s, 1H), 7.78 (d, 1H, J=7.8 Hz).

Workup

  1. stirringthe mixture was stirred at room temperature under N2 for overnight
  2. extractionfollowed by extraction with DCM (3×15 ml)
  3. dry with materialThe DCM layer was dried over Na2SO4
  4. customThe solvent was removed by distillation under the reduced pressure
  5. dissolutionThe residue was dissolved in MeOH/AcOH (4:1, 4 mL)
  6. temperatureheated at 80° C. for 2 h
  7. extractionthe aqueous layer extracted with ethyl acetate (2×30 mL)
  8. washThe combined organic extracts were washed with brine (15 mL)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-6ac2db0779ef40e3816afd56722a89a0
Source dataset
uspto-grants-2014_05
Patent number
US08722720B2

Reaction notes

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