Ammonium Chloride → 6-cyano-2,2-dimethyl-4-{1,2-dihydro-2-oxo-4-(1-hydroxy-4-p-methoxybenzyloxybutyl)-1-pyridinyl}-2H-benzo[b]pyran

HRID 487652Notes

Reaction equation

HRID 487652 reaction equation
[C:1]([C:3]1[CH:23]=[CH:22][C:6]2[O:7][C:8]([CH3:21])([CH3:20])[CH:9]=[C:10]([N:11]3[CH:16]=[CH:15][C:14]([CH:17]=[O:18])=[CH:13][C:12]3=[O:19])[C:5]=2[CH:4]=1)#[N:2].[Mg].Br[CH2:26][CH2:27][CH2:28][O:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1.[Cl-].[NH4+]>O1CCCC1>[C:1]([C:3]1[CH:23]=[CH:22][C:6]2[O:7][C:8]([CH3:20])([CH3:21])[CH:9]=[C:10]([N:11]3[CH:16]=[CH:15][C:14]([CH:17]([OH:18])[CH2:26][CH2:27][CH2:28][O:29][CH2:30][C:31]4[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=4)=[CH:13][C:12]3=[O:19])[C:5]=2[CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 110215771-Bromo-3-[(4-methoxybenzyl)oxy]propaneHCID 190925656-cyano-2,2-dimethyl-4-(1,2-dihydro-2-oxo-4-formyl-1-pyridinyl)-2H-benzo[b]pyran

Product 1

HCID 190925076-cyano-2,2-dimethyl-4-{1,2-dihydro-2-oxo-4-(1-hydroxy-4-p-methoxybenzyloxybutyl)-1-pyridinyl}-2H-benzo[b]pyranYield 58.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Forty milliliters of an anhydrous tetrahydrofuran solution containing 1.53 g of 6-cyano-2,2-dimethyl-4-(1,2-dihydro-2-oxo-4-formyl-1-pyridinyl)-2H-benzo[b]pyran, obtained in Example 25, is added at 0° C. to a Grignard reagent solution prepared from 0.19 g of magnesium and 1.94 g of 1-bromo-3-p-methoxybenzyloxy propane in 5 ml anhydrous tetrahydrofuran, and the resulting mixture is reacted first at that temperature for 10 minutes and then at room temperature for one hour. After stopping the reaction by adding a saturated aqueous solution of ammonium chloride, the reaction mixture is extracted with ethyl acetate. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The inorganic matter is filtered off and the filtrate is concentrated under reduced pressure. The residue is purified by silica gel column chromatography using 1/1 mixture of ethyl acetate/methylene chloride as a developing solvent. Thus, 1.43 g of 6-cyano-2,2-dimethyl-4-{1,2-dihydro-2-oxo-4-(1-hydroxy-4 -p-methoxybenzyloxybutyl)-1-pyridinyl}-2H-benzo[b]pyran is obtained.

Workup

  1. customobtained in Example 25
  2. customthe resulting mixture is reacted first at that temperature for 10 minutes
  3. customthe reaction
  4. extractionthe reaction mixture is extracted with ethyl acetate
  5. washThe organic layer is washed with saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe inorganic matter is filtered off
  8. concentrationthe filtrate is concentrated under reduced pressure
  9. customThe residue is purified by silica gel column chromatography
  10. addition1/1 mixture of ethyl acetate/methylene chloride as a developing solvent

Sources & evidence

ORD record
ord-c30e598a3a8b4999a7a488d112557e2c
Source dataset
uspto-grants-1994_03
Patent number
US05296492

Reaction notes

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