Sodium Bicarbonate → N-[(S)-2-(3,4-Dichlorophenyl)-4-hydroxybutyl]-N-methyl-3-cyano-1-naphthamide

HRID 1355381Notes

Reaction equation

HRID 1355381 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:12][CH2:13][OH:14])[CH2:10][NH2:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:15](=O)(O)[O-].[Na+].[C:20]([C:22]1[CH:23]=[C:24]([C:32](Cl)=[O:33])[C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2)#[N:21]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:12][CH2:13][OH:14])[CH2:10][N:11]([CH3:15])[C:32]([C:24]2[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:31]=[C:22]([C:20]#[N:21])[CH:23]=2)=[O:33])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 20794251(gammaS)-gamma-(Aminomethyl)-3,4-dichlorobenzenepropanolHCID 226366863-Cyano-1-naphthoyl chloride

Product 1

HCID 53679342N-[(S)-2-(3,4-Dichlorophenyl)-4-hydroxybutyl]-N-methyl-3-cyano-1-naphthamideYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(S)-2-(3,4-Dichlorophenyl)-4-hydroxybutylamine (20.8 g, 83.8 mmol) was dissolved in DCM (700 mL). To the stirred solution was added 10% aqueous sodium bicarbonate (300 mL), and the mixture cooled to 0° C. A solution of 3-cyano-1-naphthoyl chloride (17.4 g, 80.6 mmol) in DCM (300 mL) was added dropwise over 30 minutes. The mixture was then allowed to warm to ambient temperature and stir for 20 h. The layers were separated, and the aqueous phase washed with DCM (300 mL). The combined organic layers were dried (Na2SO4), filtered, and evaporated in vacuo to give a white foam. Purification by chromatography (silica gel; 0-25% acetonitrile in DCM) provided the desired product as a white foam (27.0 g, 78%). 1H-NMR (DMSO-d6) δ1.46-1.60 (m, 1H, CH); 1.77-1.91 (m, 3H, CH); 4.38-4.41 (t, 1H, CH); 4.54-4.57 (t, 2H, CH); 6.43 (broad, 1H, OH); 6.84-7.26 (m, 2H, aromatic); 7.44-7.54 (m, 3H, aromatic); 7.57-7.80 (m, 7H, aromatic); 8.04-8.33 (m, 2H, aromatic); 8.61 (s, 1H, aromatic).

Workup

  1. temperatureto warm to ambient temperature
  2. customThe layers were separated
  3. washthe aqueous phase washed with DCM (300 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto give a white foam
  8. customPurification by chromatography (silica gel; 0-25% acetonitrile in DCM)

Sources & evidence

ORD record
ord-4ad19378555c4a838fd6174da7082420
Source dataset
uspto-grants-2003_07
Patent number
US06586432B2

Reaction notes

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