Phosphorus oxychloride → 2-Chloro-6-{[1-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)ethylidene]amino}benzonitrile

HRID 540312

Reaction equation

HRID 540312 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][CH2:9][CH2:8][N:7]1[C:17](=O)[CH3:18].[NH2:20][C:21]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:22]=1[C:23]#[N:24].C(=O)(O)[O-].[Na+]>ClCCl.O>[Cl:29][C:25]1[CH:26]=[CH:27][CH:28]=[C:21]([N:20]=[C:17]([N:7]2[CH2:8][CH2:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH2:6]2)[CH3:18])[C:22]=1[C:23]#[N:24]

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 810562-Amino-6-chlorobenzonitrileHCID 516892Sodium BicarbonateHCID 104651101-(1,3,4,5-Tetrahydro-2H-2-benzazepin-2-yl)ethanone

Product 1

HCID 712545892-Chloro-6-{[1-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)ethylidene]amino}benzonitrileYield 63.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Phosphorus oxychloride (2.93 mL, 32.0 mmol) was added to a stirred solution of 1-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)ethanone (5.5 g, 29.0 mmol) in dry dichloromethane (100 mL) at 10° C. After that, the mixture was stirred for 20 minutes at room temperature. Then a solution of 2-amino-6-chloro-benzonitrile (4.43 g, 29.0 mmol) in dry dichloromethane (40 mL) was added and the resulting suspension was heated under reflux for 24 hours. After the reaction mixture was cooled to room temperature, water (50 mL) was added followed by saturated sodium bicarbonate to pH 8. The organic layer was separated and the aqueous was extracted with dichloromethane (100 mL). The organic fraction was washed with brine and dried over sodium sulfate, and then evaporated in vacuo to give a residue which was precipitated in ether. The solid was collected by filtration and dried in vacuo to give 6 g of product as a brown powder (yield was 63.7%). It was used in the next step without further purification. MS obsd. (ESI+) [(M+H)+] 324.

Workup

  1. temperaturethe resulting suspension was heated
  2. temperatureunder reflux for 24 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. customThe organic layer was separated
  5. extractionthe aqueous was extracted with dichloromethane (100 mL)
  6. washThe organic fraction was washed with brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated in vacuo
  9. customto give a residue which
  10. customwas precipitated in ether
  11. filtrationThe solid was collected by filtration
  12. customdried in vacuo

Sources & evidence

ORD record
ord-1a12b80a46b04bebbaefe099bf976c4b
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Linked notes

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