Chloroacetyl chloride → N-(2-(5-bromo-2-fluorophenyl)-3,3-difluoro-4-hydroxybutan-2-yl)-2-chloroacetamide
Reaction equation
[NH2:1][C:2]([C:9]1[CH:14]=[C:13]([Br:15])[CH:12]=[CH:11][C:10]=1[F:16])([CH3:8])[C:3]([F:7])([F:6])[CH2:4][OH:5].C([O-])([O-])=O.[Na+].[Na+].[Cl:23][CH2:24][C:25](Cl)=[O:26].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CO>[Br:15][C:13]1[CH:12]=[CH:11][C:10]([F:16])=[C:9]([C:2]([NH:1][C:25](=[O:26])[CH2:24][Cl:23])([C:3]([F:6])([F:7])[CH2:4][OH:5])[CH3:8])[CH:14]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To an ice cooled solution of 3-amino-3-(5-bromo-2-fluorophenyl)-2,2-difluorobutan-1-ol (3.1 g, 10.4 mmol), in DCM (60 ml) was added aqueous Na2CO3 (2.74 g, 25.8 mmol in 7.0 mL H2O) and stirred for 10 min. Chloroacetyl chloride (0.986 ml, 11.4 mmol) was then added to the resultant reaction mixture and stirring continued for 30 min at 0° C. Upon formation of the new product by TLC analysis, K2CO3 (1.5 g, 10.4 mmol) in MeOH (17 mL) was added to the reaction mixture and stirred at rt for 30 min. The reaction mixture was diluted with DCM, separated the organic layer and washed successively with water and brine solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure to furnish title compound as a colorless gum. Yield=3.3 g (78.5%).
Workup
- customreaction mixture
- stirringstirring
- waitcontinued for 30 min at 0° C
- stirringstirred at rt for 30 min
- customseparated the organic layer
- washwashed successively with water and brine solution
- dry with materialdried over anhydrous Na2SO4
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-e8283ddf22e8429ebaa28f3e718fc83b
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08207164B2
Reaction notes
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