Boron tribromide → 5-Amino-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-2'-ol

HRID 455647Notes

Reaction equation

HRID 455647 reaction equation
[F:1][C:2]1[C:15]2[O:14][C:13]3[C:8](=[CH:9][C:10]([C:16]4[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=4)=[CH:11][CH:12]=3)[C:7]3([N:27]=[C:26]([NH2:28])[CH2:25][O:24][CH2:23]3)[C:6]=2[CH:5]=[C:4]([O:29]C)[CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:28][C:26]1[CH2:25][O:24][CH2:23][C:7]2([C:6]3[CH:5]=[C:4]([OH:29])[CH:3]=[C:2]([F:1])[C:15]=3[O:14][C:13]3[C:8]2=[CH:9][C:10]([C:16]2[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:11][CH:12]=3)[N:27]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 674375114'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

Product 1

HCID 674401225-Amino-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-2'-olYield 95.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (1.668 g, 4.07 mmol) in DCM (12 ml) was added boron tribromide (0.963 mL, 10.19 mmol). Stirring was continued for 45 hrs at 0° C. at which point the mixture was removed from the bath and stirred for 2 hrs at RT. The reaction mixture was recooled to 0° C. and quenched by careful addition of saturated aqueous NaHCO3 solution (˜10 mL). The mixture became colorless with a white precipitate. The solvent was removed in vacuo, the mixture was diluted with water and filtered. The solid was washed with water and dried on air for 2 hrs, then for 2 hrs in high vacuum at RT to afford 5-amino-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-2′-ol (1.53 g, 3.87 mmol, 95% yield).

Workup

  1. customthe mixture was removed from the bath
  2. stirringstirred for 2 hrs at RT
  3. customwas recooled to 0° C.
  4. customquenched by careful addition of saturated aqueous NaHCO3 solution (˜10 mL)
  5. customThe solvent was removed in vacuo
  6. additionthe mixture was diluted with water
  7. filtrationfiltered
  8. washThe solid was washed with water
  9. customdried on air for 2 hrs

Sources & evidence

ORD record
ord-f8a9c0eef6b2406dbbc235d5f236df1d
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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