Phenol → 4-[4-(4-Fluorophenyl)-2-methyl-5-(2-phenoxy-pyrimidin-4-yl)-3-oxo-2,3-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl ester

HRID 1838868Notes

Reaction equation

HRID 1838868 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([N:23]2[C:27]([C:28]3[CH:33]=[CH:32][N:31]=[C:30](S(C)(=O)=O)[N:29]=3)=[C:26]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[C:25](=[O:45])[N:24]2[CH3:46])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]>C1COCC1>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([N:23]2[C:27]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([O:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[N:29]=3)=[C:26]([C:38]3[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=3)[C:25](=[O:45])[N:24]2[CH3:46])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 600611314-[4-(4-Fluorophenyl)-2-methyl-5-(2-methanesulfonyl-pyrimidin-4-yl)-3-oxo-2,3-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl ester

Product 1

HCID 600611364-[4-(4-Fluorophenyl)-2-methyl-5-(2-phenoxy-pyrimidin-4-yl)-3-oxo-2,3-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of phenol (0.11 g, 1.16 mmol) in THF (5 mL) is added NaH (0.024 g of a 60% dispersion in mineral oil, 0.58 mmol). After stirring for 5 min at room temp, a solution of 4-[4-(4-fluorophenyl)-2-methyl-5-(2-methanesulfonyl-pyrimidin-4-yl)-3-oxo-2,3-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl ester, 12, (0.154 g, 0.29 mmol) in THF (3 mL) is added all at once. The reaction mixture is stirred at room temp for 14 hours and then quenched by pouring into aqueous saturated NaHCO3 solution. The aqueous phase is extracted three times with CH2Cl2, the combined organic phases washed with saturated sodium bicarbonate, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was used without further purification in the next step.

Workup

  1. stirringThe reaction mixture is stirred at room temp for 14 hours
  2. customquenched
  3. additionby pouring into aqueous saturated NaHCO3 solution
  4. extractionThe aqueous phase is extracted three times with CH2Cl2
  5. washthe combined organic phases washed with saturated sodium bicarbonate
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was used without further purification in the next step

Sources & evidence

ORD record
ord-f0c998f041224ff1b9a7ec40fb1a4d4a
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

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