Hydrochloric Acid → 3-[(S)-1-(4-Bromo-phenyl)-ethyl]-1-oxa-3-aza-spiro[5.5]undecane-2,9-dione

HRID 1615165Notes

Reaction equation

HRID 1615165 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([C@@H:20]([NH:22][CH2:23][CH2:24][C:25]2([OH:38])[CH2:37][CH2:36][C:28]3([O:33]CC(C)(C)CO3)[CH2:27][CH2:26]2)[CH3:21])=[CH:16][CH:15]=1.C(N(C(C)C)C(C)C)C.Cl>ClCCl.CC(C)=O>[Br:13][C:14]1[CH:15]=[CH:16][C:17]([C@@H:20]([N:22]2[CH2:23][CH2:24][C:25]3([CH2:26][CH2:27][C:28](=[O:33])[CH2:36][CH2:37]3)[O:38][C:2]2=[O:4])[CH3:21])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 679962089-{2-[(S)-1-(4-bromo-phenyl)-ethylamino]-ethyl}-3,3-dimethyl-1,5-dioxa-spiro[5.5]undecan-9-ol

Product 1

HCID 565957523-[(S)-1-(4-Bromo-phenyl)-ethyl]-1-oxa-3-aza-spiro[5.5]undecane-2,9-dione

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

Triphosgene (2.51 g) is added to a solution of 9-{2-[(S)-1-(4-bromo-phenyl)-ethylamino]-ethyl}-3,3-dimethyl-1,5-dioxa-spiro[5.5]undecan-9-ol (4.00 g) and ethyl-diisopropyl-amine (1.7 mL) in dichloromethane (40 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at room temperature overnight. Water is added and the organic phase is separated. The organic phase is dried (Na2SO4) and concentrated to give an oil that is dissolved in acetone (20 mL). 1 M Hydrochloric acid (19 mL) is added and the solution is stirred at room temperature for 3 h. The acetone is then evaporated, and the residue is diluted with saturated aqueous K2CO3 solution and extracted with ethyl acetate. The combined extracts are washed with water and brine, dried (MgSO4), and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 1:1→0:1) to give the title compound. Yield: 1.89 g (52% of theory); LC (method 8): tR=1.27 min; Mass spectrum (ESI+): m/z=366/368 (Br) [M+H]+.

Workup

  1. temperaturechilled in an ice bath
  2. customThe cooling bath is removed
  3. additionWater is added
  4. customthe organic phase is separated
  5. dry with materialThe organic phase is dried (Na2SO4)
  6. concentrationconcentrated
  7. customto give an oil that
  8. stirringthe solution is stirred at room temperature for 3 h
  9. customThe acetone is then evaporated
  10. additionthe residue is diluted with saturated aqueous K2CO3 solution
  11. extractionextracted with ethyl acetate
  12. washThe combined extracts are washed with water and brine
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated
  15. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 1:1→0:1)

Sources & evidence

ORD record
ord-ff69e76718b9468c89024f46676b152b
Source dataset
uspto-grants-2014_07
Patent number
US08765744B2

Reaction notes

Loading…