Acetic Anhydride → HCID 58550744, compound

HRID 1908069Notes

Reaction equation

HRID 1908069 reaction equation
[F:1][C:2]1[C:7]2[N:8]3[C:25]([CH:26]=O)=[CH:24][CH:23]=[C:9]3[C:10]3([CH2:16][CH2:15][N:14]([C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH2:13][CH2:12]3)[O:11][C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl.[NH2:29]O.C([O-])(=O)C.[Na+].CC(OC(C)=O)=O.C([O-])(O)=O.[Na+]>C(O)C.O>[F:1][C:2]1[C:7]2[N:8]3[C:25]([C:26]#[N:29])=[CH:24][CH:23]=[C:9]3[C:10]3([CH2:12][CH2:13][N:14]([C:17](=[O:22])[C:18]([F:19])([F:20])[F:21])[CH2:15][CH2:16]3)[O:11][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 58551192HCID 58551192, compound

Product 1

HCID 58550744HCID 58550744, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 9′-fluoro-1-(2,2,2-trifluoroacetyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1′-carbaldehyde (715 mg, 1.9 mmol) in ethanol (3.5 mL) heated at 70° C. was added an aqueous solution of hydroxylamine hydrochloride (587 mg, 8.4 mmol) and sodium acetate (1.16 g, 14.20 mmol) in water (3.6 mL). The mixture was heated at 60° C. for 2 h. The mixture was cooled to 25° C., water added and the precipitate formed was collected by filtration and washed thoroughly with water and dried under vacuum. The residue was dissolved in Ac2O (3.37 mL, 35.74 mmol) and heated at 140° C. for 5 h. The reaction was cooled down to 25° C., poured onto ice, basified by addition of NaHCO3 (solid) until no more foaming occurred and was extracted with dichloromethane (3×5 mL). The combined organic phases were dried, filtered and concentrated to yield a residue that was purified by silica gel chromatography (gradient: 0.5-45% EtOAc in hexanes) to yield 9-fluoro-1′-(2,2,2-trifluoroacetyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbonitrile (50 mg, 7%). ESI-MS m/z calc. 379.1. found 380.3 (M+1)+; Retention time 1.82 minutes (3 min run).

Workup

  1. temperatureThe mixture was cooled to 25° C.
  2. customthe precipitate formed
  3. filtrationwas collected by filtration
  4. washwashed thoroughly with water
  5. customdried under vacuum
  6. temperatureheated at 140° C. for 5 h
  7. temperatureThe reaction was cooled down to 25° C.
  8. additionpoured onto ice
  9. extractionwas extracted with dichloromethane (3×5 mL)
  10. customThe combined organic phases were dried
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto yield a residue that
  14. customwas purified by silica gel chromatography (gradient: 0.5-45% EtOAc in hexanes)

Sources & evidence

ORD record
ord-fc39394d8b2643bfa0c0763395a1a594
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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