Hydrochloric Acid → 4-Cyclopropyl-2-fluoroaniline

HRID 1433798Notes

Reaction equation

HRID 1433798 reaction equation
NC(C1C=CC(OCCO[Si](C)(C)C)=CC=1)C(NC(C(C1C=CC=CC=1)C)C([NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:18][CH2:17]2)=[CH:12][C:11]=1[F:19])=O)=O.N1C=CC=CC=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.Cl>ClCCl>[CH:16]1([C:13]2[CH:14]=[CH:15][C:10]([NH2:9])=[C:11]([F:19])[CH:12]=2)[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 94429TriphosgeneHCID 68619166HCID 68619166, compound

Product 1

HCID 201000714-Cyclopropyl-2-fluoroanilineYield 82.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-{2-Amino-2-[4-(2-trimethylsilanyloxy-ethoxy)-phenyl]-acetylamino}-N-(4-cyclopropyl-2-fluorophenyl)-3-phenyl-butyramide (680 mg, 1.2 mmol) and pyridine (3 mL) were dissolved in dichloromethane (60 mL) at −78° C. To this mixture was added a solution of triphosgene (296 mg, 1 mmol) in dichloromethane (15 mL) dropwise. The mixture was allowed to slowly warm to room temperature and stirred overnight at room temperature. The mixture was cooled in an ice bath and 3 M HCl (60 mL) was added slowly and stirring was continued at 0° C. for 30 minutes. The organic layer was separated and dried over anhydrous sodium sulfate. Concentration gave 150 mg of a oily solid that was chromatographed over silica gel (65% v/v ethyl acetate in hexanes) to give N-(4-cyclopropyl-2-fluoro-phenyl)-2-{4-[4-(2-hydroxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1yl}-3-phenyl-butyramide as a yellow solid (70 mg, 0.13 mmol, 13%).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. stirringstirring
  3. waitwas continued at 0° C. for 30 minutes
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationConcentration

Sources & evidence

ORD record
ord-0734eda2319d45969e5417bad27d94dc
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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