Ammonia → US8975415, RP1a

HRID 873743Notes

Reaction equation

HRID 873743 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[O:12][CH2:11][C:6]1([CH2:10][CH2:9][CH2:8][O:7]1)[C:5]2=[CH2:16].II.C[CH2:20][OH:21].[NH3:22].CC#[N:25]>CCOC(C)=O.C1COCC1.[Ag]OC#N>[Br:1][C:2]1[CH:3]=[C:4]2[C:5]3([CH2:16][O:21][C:20]([NH2:25])=[N:22]3)[C:6]3([CH2:10][CH2:9][CH2:8][O:7]3)[CH2:11][O:12][C:13]2=[CH:14][CH:15]=1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 702EthanolHCID 807IodineHCID 6342AcetonitrileHCID 867242926-bromo-4-methylene-4',5'-dihydro-3'H,4H-spiro[chromene-3,2'-furan]

Product 1

HCID 86724291US8975415, RP1a

Reagents, catalysts & solvents 3

HCID 178513473HCID 178513473, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To an ice chilled solution of 6-bromo-4-methylene-4′,5′-dihydro-3′H,4H-spiro[chromene-3,2′-furan] (497 mg, 1.77 mmol) in EtOAc (2.5 ml) and MeCN (2.5 ml) was added silver cyanate (397 mg, 2.65 mmol) in an ice bath under an argon atmosphere. To the mixture was added iodine (673 mg, 2.65 mmol). After stirring for 30 minutes in the ice bath and 30 minutes at ambient temperature, the mixture was filtered through celite. The filtrate was washed with saturated aqueous Na2S2O3. The organic layer was washed with brine, dried over Na2SO4, filtered, and the filtrate was evaporated to give an oil. The oil was dissolved in THF (5 mL) and a 2M EtOH solution of NH3 (4.5 ml, 9.0 mmol) was added under ice bath cooling. The mixture was stirred overnight under ice bath cooling and for 1 hour at 70° C. After concentration in vacuo, the residue was diluted with saturated aqueous NaHCO3 and extracted with CHCl3. The organic layer was washed with brine, dried over Na2SO4, filtered, and the filtrate was evaporated off. The residue was purified by silica gel chromatography(CHCl3/EtOH=100:0-90:10) to give less polar diastereomer of 6′-bromo-4,5-dihydro-3H-dispiro[furan-2,3′-chromene-4′,4″-[1,3]oxazol]-2″-amine (178 mg) and polar diastereomer of 6′-bromo-4,5-dihydro-3H-dispiro[furan-2,3′-chromene-4′,4″-[1,3]oxazol]-2″-amine (367 mg).

Workup

  1. filtrationthe mixture was filtered through celite
  2. washThe filtrate was washed with saturated aqueous Na2S2O3
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe filtrate was evaporated
  7. customto give an oil
  8. temperaturecooling
  9. concentrationAfter concentration in vacuo
  10. additionthe residue was diluted with saturated aqueous NaHCO3
  11. extractionextracted with CHCl3
  12. washThe organic layer was washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. customthe filtrate was evaporated off
  16. customThe residue was purified by silica gel chromatography(CHCl3/EtOH=100:0-90:10)

Sources & evidence

ORD record
ord-53446176c3df4aeb9b5da406746a89eb
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

Loading…