Chloroacetyl chloride → N-benzyl-2-chloro-N-[(3RS)-3-(3,4-dichlorophenyl)-3-hydroxy-4-(4-methoxyphenoxy)butyl]acetamide

HRID 1022587Notes

Reaction equation

HRID 1022587 reaction equation
[CH2:1]([NH:8][CH2:9][CH2:10][C:11]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)([OH:22])[CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:38][CH2:39][C:40](Cl)=[O:41]>C1COCC1.O>[CH2:1]([N:8]([CH2:9][CH2:10][C:11]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)([OH:22])[CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:40](=[O:41])[CH2:39][Cl:38])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 669749564-(Benzylamino)-2-(3,4-dichlorophenyl)-1-(4-methoxyphenoxy)butan-2-ol

Product 1

HCID 66976486N-benzyl-2-chloro-N-[(3RS)-3-(3,4-dichlorophenyl)-3-hydroxy-4-(4-methoxyphenoxy)butyl]acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

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. stirringstirred
  2. temperaturewhile warming to room temperature for 2 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. extractionThe obtained extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-894d03c3ef274b20a7642a4e7a6033c2
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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