Chloroacetyl chloride → (+/-)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide

HRID 1430905Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([N:11]2[CH2:16][CH2:15][C@@H:14]([NH2:17])[C@H:13]([OH:18])[CH2:12]2)[C:9]=1[Cl:10])[C:5]#[N:6].C([O-])(=O)C.[K+].[Cl:24][CH2:25][C:26](Cl)=[O:27]>CC(C)=O.O>[NH2:1][C:2]1[C:9]([Cl:10])=[C:8]([N:11]2[CH2:16][CH2:15][C@@H:14]([NH:17][C:26](=[O:27])[CH2:25][Cl:24])[C@H:13]([OH:18])[CH2:12]2)[CH:7]=[C:4]([C:5]#[N:6])[CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

(+/−)-3-amino-5-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-4-chlorobenzonitrile (prepared from Example 171D) (1.0 g, 3.75 mmol) and potassium acetate (0.736 g, 7.50 mmol) were dissolved in acetone (20 ml)+water (6 mL). The solution was cooled to 0° C. under nitrogen. Chloroacetic chloride (0.373 ml, 4.69 mmol) was added dropwise and the mixture stirred at 0° C. for 10 minutes, then at room temperature for 60 minutes. The reaction mixture was partitioned between EtOAc and aq. NaHCO3 solution. The organic layer was washed with brine and dried over MgSO4. MgSO4 was removed by filtration and volatiles evaporated in vacuum to afford (+/−)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide (0.61 g,); The material was used without further purification.

Workup

waitat room temperature for 60 minutes
customThe reaction mixture was partitioned between EtOAc and aq. NaHCO3 solution
washThe organic layer was washed with brine
dry with materialdried over MgSO4
customMgSO4 was removed by filtration and volatiles
customevaporated in vacuum

Sources & evidence

ORD record: ord-4cd9ba229e34441f8ec0522a3c120e76
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940736B2

Reaction notes

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