Sodium hydride → 7-Chloro-6-(1,4-dioxa-spiro[4.5]dec-8-yloxy)-2-(4-methoxy-benzyl)-2H-isoquinolin-1-one

HRID 2370287Notes

Reaction equation

HRID 2370287 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)CCO1.[H-].[Na+].[Cl:14][C:15]1[CH:24]=[C:23]2[C:18]([CH:19]=[CH:20][N:21]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[C:22]2=[O:25])=[CH:17][C:16]=1F.[CH3:36][C:37](N(C)C)=[O:38]>>[Cl:14][C:15]1[CH:24]=[C:23]2[C:18]([CH:19]=[CH:20][N:21]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[C:22]2=[O:25])=[CH:17][C:16]=1[O:11][CH:8]1[CH2:7][CH2:6][C:5]2([O:1][CH2:36][CH2:37][O:38]2)[CH2:10][CH2:9]1

Participants

5

Reactant 4

HCID 24758Sodium hydrideHCID 31374Dimethylacetamide2×HCID 598182477-Chloro-6-fluoro-2-[(4-methoxyphenyl)methyl]isoquinolin-1(2H)-oneHCID 86623504Dioxa-spiro[4.5]decan-8-ol

Product 1

HCID 592260607-Chloro-6-(1,4-dioxa-spiro[4.5]dec-8-yloxy)-2-(4-methoxy-benzyl)-2H-isoquinolin-1-one

Procedure

1.49 g (9.44 mmol) of dioxa-spiro[4.5]decan-8-ol were dissolved in 30 ml of dimethyl acetamide and 283 mg (11.8 mmol) of sodium hydride (60%) were added. After stirring for 30 min at room temperature a solution of 2.50 g (7.87 mmol) of 7-chloro-6-fluoro-2-(4-methoxy-benzyl)-2H-isoquinolin-1-one (10) in 20 ml of dimethyl acetamide was added and stirring was continued at room temperature. After the reaction went to completion the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and washed with water. The organic layer was dried with magnesium sulfate and evaporated. Purification by silica gel chromatography yielded 1.84 g of the title compound. Rt=2.00 min (Method B). Detected mass: 456.1 (M+H+).

Workup

  1. additionwas added
  2. customwas continued at room temperature
  3. customwas removed under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane
  5. washwashed with water
  6. dry with materialThe organic layer was dried with magnesium sulfate
  7. customevaporated
  8. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-0de23a87067a4fe1896378e4471efaa6
Source dataset
uspto-grants-2014_04
Patent number
US08710077B2

Reaction notes

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