Bromoacetyl bromide → 2-bromo-N-(2-chloro-5-cyano-3-nitrophenyl)acetamide

HRID 921866Notes

Reaction equation

HRID 921866 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[C:9]=1[Cl:10])[C:5]#[N:6].[Br:14][CH2:15][C:16](Br)=[O:17]>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[Br:14][CH2:15][C:16]([NH:1][C:2]1[CH:3]=[C:4]([C:5]#[N:6])[CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[C:9]=1[Cl:10])=[O:17]

Participants

5

Reactant 2

HCID 61147Bromoacetyl bromideHCID 717559993-Amino-4-chloro-5-nitrobenzonitrile

Product 1

HCID 899223412-bromo-N-(2-chloro-5-cyano-3-nitrophenyl)acetamideYield 103.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of 3-amino-4-chloro-5-nitrobenzonitrile (300 mg, 1.518 mmol) in DCM (10 mL) at 0° C. was added TEA (0.317 mL, 2.278 mmol) and then 2-bromoacetyl bromide (0.145 mL, 1.670 mmol) was added drop wise. The reaction mixture was stirred at 0° C. for 3 h. LC-MS indicated a new peak. Then it was diluted with DCM and saturated aqueous sodium bicarbonate solution was added. After separating the layers, the aqueous layer was further extracted with DCM. The combined organic extracts were washed with water, brine, dried over MgSO4, filtered and concentrated. The crude was used in the next step without purification. To a solution of above obtained crude 2-bromo-N-(2-chloro-5-cyano-3-nitrophenyl)acetamide (500 mg, 1.570 mmol) in DCM (4 mL) was added TEA (0.438 mL, 3.14 mmol) then a solution of 2-(methylamino)ethanol (118 mg, 1.570 mmol) in THF (4 mL) was added slowly. After stirring at room temperature for 1 h, LC-MS indicated completion. After concentration purification via flash chromatography (0-5% MeOH in DCM, 12 g) gave N-(2-chloro-5-cyano-3-nitrophenyl)-2-((2-hydroxyethyl)(methyl)amino)acetamide (170 mg) as a yellow oil, MS (ESI+) m/z 313.0

Workup

  1. additionwas added
  2. customAfter separating the layers
  3. extractionthe aqueous layer was further extracted with DCM
  4. washThe combined organic extracts were washed with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was used in the next step without purification

Sources & evidence

ORD record
ord-951965a432334c71a7135b78ebe113b0
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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