Chloroacetone → (S)-1-(2-amino-2'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)propan-2-one

HRID 1970366Notes

Reaction equation

HRID 1970366 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:26]=1)[C:18]1[CH:17]=[C:16]([OH:19])[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)=[CH:9][CH:10]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:34][C:35]([CH3:37])=[O:36]>CN(C=O)C>[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:26]=1)[C:6]1[CH:7]=[C:8]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[CH:9]=[CH:10][C:11]=1[O:12][C:13]1[C:18]2=[CH:17][C:16]([O:19][CH2:34][C:35](=[O:36])[CH3:37])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 6571Chloroacetone3×HCID 10796Cesium carbonate2×HCID 58466221(S)-2-amino-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2'-ol

Product 1

HCID 67243382(S)-1-(2-amino-2'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)propan-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A vial was charged with (S)-2-amino-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (0.300 g, 0.869 mmol), cesium carbonate (0.425 g, 1.303 mmol). DMF (3.47 mL) was added, the vial was sonicated for 30 s, and the mixture was stirred vigorously for 20 min, at which time some white solid still remained. The vial was cooled in an ice-bath for 10 min, then 1-chloroacetone (0.083 mL, 1.042 mmol) was added dropwise and the reaction was stirred over the weekend, during which the bath warmed to RT. The reaction was cooled back to 0° C. and 1-chloroacetone (0.083 mL, 1.042 mmol) was added. The reaction was stirred for two hours before 0.5 equivalents of cesium carbonate and chloroacetone were added at one hour intervals until the reaction was complete. The mixture was partitioned between water and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The material was purified via column chromatography (RediSep 40 g, gradient elution 0-5% MeOH:DCM) to afford (S)-1-(2-amino-2′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yloxy)propan-2-one as a white solid. The remaining fractions were combined and concentrated to afford impure material as an off-white solid.

Workup

  1. customthe vial was sonicated for 30 s
  2. temperatureThe vial was cooled in an ice-bath for 10 min
  3. stirringthe reaction was stirred over the weekend, during which the bath
  4. temperatureThe reaction was cooled back to 0° C.
  5. additionwere added at one hour intervals until the reaction
  6. customThe mixture was partitioned between water and EtOAc
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with EtOAc (2×)
  9. dry with materialThe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe material was purified via column chromatography (RediSep 40 g, gradient elution 0-5% MeOH:DCM)

Sources & evidence

ORD record
ord-819c2d4b8483472f903758b8dcdbb1e6
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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