Hydrochloric Acid → N-(2-Chloro-4-cyano-6-methylphenyl)acetamide

HRID 1819681Notes

Reaction equation

HRID 1819681 reaction equation
[NH2:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[Cl:11].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:22](Cl)(=[O:24])[CH3:23].Cl>C1COCC1.O.C(Cl)Cl>[C:22]([NH:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[Cl:11])(=[O:24])[CH3:23]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27353014-Amino-3-chloro-5-methylbenzonitrile

Product 1

HCID 58962910N-(2-Chloro-4-cyano-6-methylphenyl)acetamideYield 34%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Step G (1). To a stirred solution of 4-amino-3-chloro-5-methylbenzonitrile (0.516 g, 3.1 mmol) in 10 mL of THF at rt was added 6.6 mL of 1.0 M NaHMDS in THF. The resulting reaction mixture was stirred at rt for 30 min., at which time acetyl chloride (3.1 mmol) was added. CH2Cl2 (100 mL) and water (100 mL) were added to the reaction mixture after being stirred overnight, followed by the addition of 5 mL of 1.4 N HCl aqueous solution. Layers were separated and the aqueous layer was extracted with CH2Cl2 (2×100 mL). The extracts were combined and solvents were evaporated in vacuo. The residue was purified by flash chromatography (5-20% EtOAc/DCM) to give 0.220 g of 4-acetamido-3-chloro-5-methylbenzonitrile. 1H NMR (500 MHz, CDCl3) δ 7.57 (s, 1 H), 7.46 (s, 1 H), 7.02 (s, 1 H), 2.31 (s, 3 H), 2.26 (s, 3 H).

Workup

  1. customThe resulting reaction mixture
  2. additionwas added
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×100 mL)
  5. customsolvents were evaporated in vacuo
  6. customThe residue was purified by flash chromatography (5-20% EtOAc/DCM)

Sources & evidence

ORD record
ord-cdef897e41974f17999b50c9158c63ab
Source dataset
uspto-grants-2009_10
Patent number
US07601751B2

Reaction notes

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