Sodium hydride → Tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methylene}piperidine-1-carboxylate

HRID 394114Notes

Reaction equation

HRID 394114 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([CH2:18]P(=O)(OCC)OCC)[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:35])[N:13]2[C:27]1[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=1[Cl:34].[H-].[Na+].[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][C:48](=O)[CH2:47][CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]>C1COCC1.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([CH:18]=[C:48]2[CH2:49][CH2:50][N:45]([C:43]([O:42][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:44])[CH2:46][CH2:47]2)[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:35])[N:13]2[C:27]1[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=1[Cl:34]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 86588158Diethyl [5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methylphosphonate

Product 1

HCID 22648188Tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methylene}piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of diethyl [5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methylphosphonate (422 mg, 0.762 mmol) in a mixture of THF (9 mL) and DMF (2 mL) at 0° C. was added sodium hydride (60%, 61 mg, 1.52 mmol). The resulting mixture was stirred at rt for 20 min and then cooled to 0° C. again. To this was added a solution of t-butyl-4-oxo-1-piperidinecarboxylate (310 mg, 1.524 mmol) in THF (2 mL). Then the reaction was stirred at rt for 22 h. The mixture was quenched with brine, and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. Removal of the solvent and subsequent purification by flash chromatography using 20% acetone/hexane as eluent provided tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methylene}piperidine-1-carboxylate as a white solid. 1H NMR (CDCl3, 500 MHz): δ 1.48 (s, 9H), 2.24 (brs, 2H), 2.31 (t, 2H, J=5.7 Hz), 3.31 (t, 2H, J=5.5 Hz), 3.45 (t, 2H, J=5.5 Hz), 4.35 (abq, 2H, J=14.4 Hz), 5.10 (s, 1H), 5.96 (s, 1H), 6.21 (s, 1H), 6.74 (s, 1H), 7.30-7.58 (m, 7H). MS (API-ES+): 600 (M+H).

Workup

  1. temperaturecooled to 0° C. again
  2. stirringThen the reaction was stirred at rt for 22 h
  3. customThe mixture was quenched with brine
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customRemoval of the solvent and subsequent purification by flash chromatography

Sources & evidence

ORD record
ord-7dc14c90f94e467d877d6d93baa2a128
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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