Acetic Anhydride → HCID 86660257, compound

HRID 1908065Notes

Reaction equation

HRID 1908065 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:26]=O)[N:5]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[O:8][C:7]3([CH2:19][CH2:18][N:17]([C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])[CH2:16][CH2:15]3)[C:6]=12.Cl.[NH2:29]O.C([O-])(=O)C.[Na+].CC(OC(C)=O)=O.C([O-])(O)=O.[Na+]>C(O)C.O>[CH3:1][C:2]1[CH:3]=[C:4]([C:26]#[N:29])[N:5]2[C:6]=1[C:7]1([CH2:15][CH2:16][N:17]([C:20](=[O:25])[C:21]([F:24])([F:22])[F:23])[CH2:18][CH2:19]1)[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]2=1

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 58551582HCID 58551582, compound

Product 1

HCID 86660257HCID 86660257, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 3′-methyl-1-(2,2,2-trifluoroacetyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1′-carbaldehyde (25 mg, 0.07 mmol) in ethanol (125 μL) at 60° C. was added an aqueous solution of hydroxylamine hydrochloride (20.7 mg, 0.30 mmol) and sodium acetate (41.2 mg, 0.50 mmol) in water (125.0 μL). The solution was stirred at 60° C. for 2 hours. The reaction was cooled to 25° C., water added and the precipitate that formed was collected by filtration. The solids were washed thoroughly with water and dried under vacuum, dissolved in Ac2O (119.1 μL, 1.26 mmol) and heated at 140° C. for 5 h. The reaction was cooled to 25° C., poured onto ice, basified by addition of solid NaHCO3 until no more foaming occurred and extracted with dichloromethane (3×5 mL). The organic phases were combined, dried, filtered and concentrated to yield a residue that was purified by silica gel chromatography using a gradient of 0.5-45% EtOAc in hexanes to yield 3-methyl-1′-(2,2,2-trifluoroacetyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbonitrile (10 mg, 40%). ESI-MS m/z calc. 375.1. found 376.3 (M+1)+; Retention time 2.01 minutes (3 min run).

Workup

  1. temperatureThe reaction was cooled to 25° C.
  2. customthe precipitate that formed
  3. filtrationwas collected by filtration
  4. washThe solids were washed thoroughly with water
  5. customdried under vacuum
  6. temperatureheated at 140° C. for 5 h
  7. temperatureThe reaction was cooled to 25° C.
  8. additionpoured onto ice
  9. extractionextracted with dichloromethane (3×5 mL)
  10. customdried
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto yield a residue that
  14. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-b44424e878d04643a77f8bc159e81386
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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