4-Benzyloxy-2(1H)-pyridone → 4-Benzyloxy-1-{2-oxo-2-[2-(2,2,2-trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinolin-7-yl]-ethyl}-1H-pyridin-2-one

HRID 564202

Reaction equation

HRID 564202 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].[I-].C([NH3+])(C)(C)C.Cl[CH2:29][C:30]([C:32]1[CH:41]=[C:40]2[C:35]([CH2:36][CH2:37][N:38]([C:42](=[O:47])[C:43]([F:46])([F:45])[F:44])[CH2:39]2)=[CH:34][CH:33]=1)=[O:31]>C1COCC1.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:29][C:30](=[O:31])[C:32]2[CH:41]=[C:40]3[C:35]([CH2:36][CH2:37][N:38]([C:42](=[O:47])[C:43]([F:46])([F:44])[F:45])[CH2:39]3)=[CH:34][CH:33]=2)[C:11](=[O:15])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 22344722t-Butylammonium IodideHCID 23665647Potassium tert-butoxideHCID 866236881-[7-(2-chloro-acetyl)-3,4-dihydro-1H-isoquinolin-2-yl]-2,2,2-trifluoro-ethanone2×

Product 1

HCID 441936264-Benzyloxy-1-{2-oxo-2-[2-(2,2,2-trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinolin-7-yl]-ethyl}-1H-pyridin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 600 mg (2.98 mmol) 4-benzyloxy-1H-pyridin-2-one in 6 mL THF is added at 0° C. 368 mg (3.28 mmol) potassium tert-butylate and 55 mg (0.15 mmol) tert-butylammonium iodide. After 5 min 1.00 g (3.28 mmol) 1-[7-(2-chloro-acetyl)-3,4-dihydro-1H-isoquinolin-2-yl]-2,2,2-trifluoro-ethanone is added. After 2 h additional 600 mg (1.97 mmol) 1-[7-(2-chloro-acetyl)-3,4-dihydro-1H-isoquinolin-2-yl]-2,2,2-trifluoro-ethanone is added and the mixture is stirred an additional hour. The reaction mixture is diluted with EtOAc and the organic phase is washed with water, filtered, dried over MgSO4 and the solvent is evaporated. The residue is purified via reverse HPLC chromatography (Zorbax stable bond; water (0.15% formic acid)/acetonitrile (0.15% formic acid) 95:5 to 5:95).

Workup

  1. washthe organic phase is washed with water
  2. filtrationfiltered
  3. dry with materialdried over MgSO4
  4. customthe solvent is evaporated
  5. customThe residue is purified via reverse HPLC chromatography (Zorbax stable bond; water (0.15% formic acid)/acetonitrile (0.15% formic acid) 95:5 to 5:95)

Sources & evidence

ORD record
ord-769f935b5fc048af99b9866c309dba05
Source dataset
uspto-grants-2011_11
Patent number
US08067590B2

Linked notes

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