Trimethylaluminum → 7'-Bromo-4'-fluoro-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 931565Notes

Reaction equation

HRID 931565 reaction equation
[NH2:1][C:2]1([CH2:20][O:21][CH2:22][C:23]#[N:24])[C:15]2[CH:14]=[C:13]([O:16][CH3:17])[CH:12]=[C:11]([F:18])[C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:19])=[CH:6][CH:7]=2.C[Al](C)C>ClCCCl>[Br:19][C:5]1[CH:4]=[C:3]2[C:8]([O:9][C:10]3[C:11]([F:18])=[CH:12][C:13]([O:16][CH3:17])=[CH:14][C:15]=3[C:2]32[N:1]=[C:23]([NH2:24])[CH2:22][O:21][CH2:20]3)=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 16682925TrimethylaluminumHCID 673828282-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)acetonitrile

Product 1

HCID 584659217'-Bromo-4'-fluoro-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amineYield 97%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)acetonitrile (7.72 g, 19.63 mmol) in DCE (115 mL) was added trimethylaluminum (2M in toluene) (19.63 mL, 39.3 mmol) at RT. The reaction mixture was stirred for 10 min at RT and then heated to 75° C. for 1 hour. The reaction mixture was cooled to RT and quenched with sodium sulfate decahydrate. The reaction mixture was vigorously stirred for 30 minutes, diluted with EtOAc and stirred overnight. The mixture was filtered through a pad of celite and filter cake was washed with EtOAc. The solvent was removed under reduced pressure to obtain an oily residue which crystallized to give 7′-bromo-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (7.49 g, 19.05 mmol, 97% yield) as a cream-colored solid.

Workup

  1. temperatureheated to 75° C. for 1 hour
  2. temperatureThe reaction mixture was cooled to RT
  3. customquenched with sodium sulfate decahydrate
  4. stirringThe reaction mixture was vigorously stirred for 30 minutes
  5. additiondiluted with EtOAc
  6. stirringstirred overnight
  7. filtrationThe mixture was filtered through a pad of celite
  8. filtrationfilter cake
  9. washwas washed with EtOAc
  10. customThe solvent was removed under reduced pressure
  11. customto obtain an oily residue which
  12. customcrystallized

Sources & evidence

ORD record
ord-0dcd847e43e847eeb80f5df2982ea768
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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