Phosgene → 3-[3-(cyclopentyloxy)-4-methoxyphenyl]-2,5-dihydro-2-methyl-5-oxo-1H-pyrazole-1-carboxamide

HRID 1612943Notes

Reaction equation

HRID 1612943 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH:5]1([O:10][C:11]2[CH:12]=[C:13]([C:19]3[N:23]([CH3:24])[NH:22][C:21](=[O:25])[CH:20]=3)[CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[CH2:9][CH2:8][CH2:7][CH2:6]1.C[Si](C)(C)[NH:28][Si](C)(C)C>O1CCCC1>[CH:5]1([O:10][C:11]2[CH:12]=[C:13]([C:19]3[N:23]([CH3:24])[N:22]([C:1]([NH2:28])=[O:2])[C:21](=[O:25])[CH:20]=3)[CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[CH2:6][CH2:7][CH2:8][CH2:9]1

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 13838HexamethyldisilazaneHCID 197927825-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,2-dihydro-1-methyl-3H-pyrazol-3-one

Product 1

HCID 197927913-[3-(cyclopentyloxy)-4-methoxyphenyl]-2,5-dihydro-2-methyl-5-oxo-1H-pyrazole-1-carboxamideYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of phosgene (8.75 mmol, 4.61 mL; 1.9M solution in toluene) in dry tetrahydrofuran (30 mL) is added 5-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,2-dihydro-1-methyl-3H-pyrazol-3-one (7.0 mmol, 2.02 g) in dry tetrahydrofuran (15 mL) dropwise over 20 minutes. The resulting cloudy solution is stirred at 0° C. for 10 minutes and at room temperature for 1 hour after which a homogenous solution is obtained. The reaction mixture is cooled to 0° C. and hexamethyldisilazane (17.5 mmol, 2.82 g; 3.64 mL) in dry tetrahydrofuran (15 mL) is added in one portion. The resulting suspension is stirred at room temperature for 1 hour and then the volatiles are removed in vacuo. The residue is partitioned between 2% aqueous acetic acid (200 mL) and ethyl acetate (200 mL) and the aqueous phase is extracted with ethyl acetate (150 mL). The combined organic layers are washed with H2O (100 mL), dried (Na2SO4), and concentrated in vacuo to afford a tan solid. This material is triturated with ether and dried in vacuo for 1 hour at 60° C. to give the title compound as a white solid (1.80 g; 78%). 1H NMR (DMSO-d6, 400 MHz) δ7.23 (br s, 1H); 7.02 (m, 3H); 6.92 (br s, 1H); 6.08 (s, 1H); 4.86 (m, 1H); 3.78 (s, 3H); 3.72 (s, 3H); 1.88 (m, 2H); 1.70 (m, 4H); 1.56 (m, 2H). IR (KBr, cm-1) 3400, 3300, 3200, 2950, 1760, 1500, 1330, 1250, 1130.

Workup

  1. customis obtained
  2. temperatureThe reaction mixture is cooled to 0° C.
  3. stirringThe resulting suspension is stirred at room temperature for 1 hour
  4. customthe volatiles are removed in vacuo
  5. customThe residue is partitioned between 2% aqueous acetic acid (200 mL) and ethyl acetate (200 mL)
  6. extractionthe aqueous phase is extracted with ethyl acetate (150 mL)
  7. washThe combined organic layers are washed with H2O (100 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford a tan solid
  11. customThis material is triturated with ether
  12. customdried in vacuo for 1 hour at 60° C.

Sources & evidence

ORD record
ord-a8cbb9e0aa06478ebd69ec3ea1822a60
Source dataset
uspto-grants-1993_03
Patent number
US05191084

Reaction notes

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