Ammonia → (RS)-4-(3-Bromophenyl)-4-(3-chloro-4-methoxyphenyl)-4,5-dihydro-oxazol-2-ylamine

HRID 1668713Notes

Reaction equation

HRID 1668713 reaction equation
II.[Br:3][C:4]1[CH:5]=[C:6]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([Cl:20])[CH:13]=2)=[CH2:11])[CH:7]=[CH:8][CH:9]=1.N.[NH2:22][C:23]([NH2:25])=[O:24]>C(OCC)(=O)C.C(#N)C.[Ag]OC#N.ClCCl>[Br:3][C:4]1[CH:5]=[C:6]([C:10]2([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([Cl:20])[CH:13]=3)[CH2:11][O:24][C:23]([NH2:25])=[N:22]2)[CH:7]=[CH:8][CH:9]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 807IodineHCID 1176UreaHCID 578250634-[1-(3-Bromo-phenyl)-vinyl]-2-chloro-1-methoxy-benzene

Product 1

HCID 57825084(RS)-4-(3-Bromophenyl)-4-(3-chloro-4-methoxyphenyl)-4,5-dihydro-oxazol-2-ylamineYield 56%

Reagents, catalysts & solvents 4

HCID 178513473HCID 178513473, compoundCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of iodine (3.76 g, 14.83 mmol) in ethyl acetate (40 mL) was added dropwise over 25 min to a mixture of 4-[1-(3-bromo-phenyl)-vinyl]-2-chloro-1-methoxy-benzene (4.36 g, 13.49 mmol) and silver cyanate (2.42 g, 16.18 mmol) in acetonitrile (38 mL) and ethyl acetate (18 mL), cooled in an ice bath. After complete addition, the reaction suspension was stirred for another 15 min at room temperature when TLC indicated the complete conversion of starting material. The reaction mixture was filtered, and the filtrate concentrated to give a dark grey oil. 80 mL of aqueous ammonia (25%) was added to the oil, and the mixture was stirred and warmed to 60° C. for 4 hours. LC-MS at this point indicated complete conversion of the intermediate urea to the desired aminoxazoline. Dichloromethane (40 mL) was added to the crude and the two phases were separated; organic layer was collected, dried over magnesium sulfate anhydrous, filtered and evaporated under reduced pressure. The solid obtained was washed with cyclohexane to give 2.89 g of desired product as a pale-yellow solid (56%)

Workup

  1. temperaturecooled in an ice bath
  2. additionAfter complete addition
  3. filtrationThe reaction mixture was filtered
  4. concentrationthe filtrate concentrated
  5. customto give a dark grey oil
  6. stirringthe mixture was stirred
  7. temperaturewarmed to 60° C. for 4 hours
  8. customthe two phases were separated
  9. customorganic layer was collected
  10. dry with materialdried over magnesium sulfate anhydrous
  11. filtrationfiltered
  12. customevaporated under reduced pressure
  13. customThe solid obtained
  14. washwas washed with cyclohexane

Sources & evidence

ORD record
ord-d0760c1e7a0c4b85938c78e42f8c35c5
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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