Benzaldehyde → 4-(Benzylamino)-2-(3,4-dichlorophenyl)-1-(4-methoxyphenoxy)butan-2-ol

HRID 1022586Notes

Reaction equation

HRID 1022586 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=1)([OH:15])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.S([O-])([O-])(=O)=O.[Mg+2].[CH:30](=O)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[BH4-].[Na+]>CO.C(N(CC)CC)C>[CH2:30]([NH:1][CH2:2][CH2:3][C:4]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=1)([OH:15])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 24083Sulfuric acid magnesium salt (1:1)HCID 4311764Sodium borohydrideHCID 66976055(2RS)-4-amino-2-(3,4-dichlorophenyl)-1-(4-methoxyphenoxy)butan-2-ol

Product 1

HCID 669749564-(Benzylamino)-2-(3,4-dichlorophenyl)-1-(4-methoxyphenoxy)butan-2-ol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of (2RS)-4-amino-2-(3,4-dichlorophenyl)-1-(4-methoxyphenoxy)butan-2-ol (6.7 g) in methanol (20 mL) were added magnesium sulfate (3.35 g), triethylamine (1.3 mL) and benzaldehyde (2.1 ml), and the mixture was stirred at room temperature for 1.5 hr. To the reaction mixture was added sodium borohydride (3.55 g), and the mixture was stirred at 0° C. for 10 min, and then stirred while warming to room temperature for 1.5 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated. The concentrated residue was diluted with water, and the mixture was extracted with ethyl acetate. The obtained extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give 4-(benzylamino)-2-(3,4-dichlorophenyl)-1-(4-methoxyphenoxy)butan-2-ol (8.47 g). To a solution of 4-(benzylamino)-2-(3,4-dichlorophenyl)-1-(4-methoxyphenoxy)butan-2-ol (8.47 g) in THF (45 mL) were added triethylamine (2.85 mL) and chloroacetyl chloride (1.64 ml), and the mixture was stirred at 0° C. for 10 min, and then stirred while warming to room temperature for 2 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The obtained extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (7.41 g).

Workup

  1. stirringthe mixture was stirred at 0° C. for 10 min
  2. stirringstirred
  3. temperaturewhile warming to room temperature for 1.5 hr
  4. filtrationThe reaction mixture was filtered through celite
  5. concentrationthe filtrate was concentrated
  6. additionThe concentrated residue was diluted with water
  7. extractionthe mixture was extracted with ethyl acetate
  8. extractionThe obtained extract
  9. washwas washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-0e9770604de94459af3b8847d93cb0c0
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

Loading…