Water → (2S)-N-{[4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}chloroacetamide

HRID 1660696Notes

Reaction equation

HRID 1660696 reaction equation
Cl.Cl.[NH2:3][CH2:4][C@@H:5]1[O:10][CH2:9][CH2:8][N:7]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[CH2:6]1.O.C(=O)([O-])O.[Na+].[Cl:26][CH2:27][C:28](Cl)=[O:29]>COC(C)(C)C>[Cl:19][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[Cl:18])[CH2:11][N:7]1[CH2:8][CH2:9][O:10][C@@H:5]([CH2:4][NH:3][C:28](=[O:29])[CH2:27][Cl:26])[CH2:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 6577Chloroacetyl chloride2×HCID 516892Sodium Bicarbonate2×HCID 57464066(S)-(4-(3,4-Dichlorobenzyl)morpholin-2-yl)methanamine dihydrochloride

Product 1

HCID 57686783(2S)-N-{[4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}chloroacetamide

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

(2S)-2-Aminomethyl-4-(3,4-dichlorobenzyl)morpholine dihydrochloride (120 g) was dissolved in tert-butyl methyl ether (450 ml), water (450 ml) was added and the mixture was cooled on an ice bath. Sodium hydrogen carbonate (95.56 g) was gradually added and, after the addition, chloroacetyl chloride (29 ml) was added dropwise over about 10 min while maintaining the inside temperature at 15° C. or below. After the completion of the dropwise addition, the mixture was stirred at room temperature for 1.5 hr. After 1.5 hr, sodium hydrogen carbonate (3 g) and chloroacetyl chloride (2.7 ml) were successively added to the reaction mixture at room temperature, and the mixture was further stirred for 1.5 hr. The reaction mixture was stood still and partitioned, and the organic layer was obtained as a solution of (2S)-N-{[4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}chloroacetamide in tert-butyl methyl ether.

Workup

  1. temperaturethe mixture was cooled on an ice bath
  2. additionwas added dropwise over about 10 min
  3. temperaturewhile maintaining the inside temperature at 15° C. or below
  4. additionAfter the completion of the dropwise addition
  5. waitAfter 1.5 hr
  6. stirringthe mixture was further stirred for 1.5 hr
  7. custompartitioned

Sources & evidence

ORD record
ord-bb2d5d2490484481b1dcf91886502af2
Source dataset
uspto-grants-2011_10
Patent number
US08030303B2

Reaction notes

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