Dichloromethane → HCID 67440104, compound

HRID 455669Notes

Reaction equation

HRID 455669 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([CH2:27][CH2:26][O:25][C:24]([NH2:28])=[N:23]3)[C:6]=2[CH:5]=[C:4]([O:29]C)[CH:3]=1.C(Cl)Cl>>[NH2:28][C:24]1[O:25][CH2:26][CH2:27][C:7]2([N:23]=1)[C:6]1[CH:5]=[C:4]([OH:29])[CH:3]=[C:2]([F:1])[C:15]=1[O:14][C:13]1[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]=1

Participants

3

Reactant 2

HCID 6344DichloromethaneHCID 67439482HCID 67439482, compound

Product 1

HCID 67440104HCID 67440104, compoundYield 99%

Procedure

To a suspension of 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine (2.178 g, 5.32 mmol) in DCM (43 mL) boron tribromide (1.509 mL, 15.96 mmol) was added dropwise at RT. The mixture was stirred 2 hrs at RT, the mixture was cooled to 0° C. and quenched by addition of 5 ml of methanol dropwise. The resulting white suspension was stirred for 20 min at 0° C., then sat. aq. NaHCO3 (˜5 ml) was added followed by addition of 25% aq. ammonia (˜15 ml). The mixture was stirred for 30 min, then DCM was removed in a stream of nitrogen. The mixture was diluted with water (10 ml) and 25% ammonia (10 ml) and filtered. The white solid was washed with water twice, then dried for 3 hrs on air, then in vacuo overnight to give 2-amino-4′-fluoro-7′-(2-fluoropyridin-3-yl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2′-ol (2.08 g, 5.26 mmol, 99% yield).

Workup

  1. additionwas added dropwise at RT
  2. temperaturethe mixture was cooled to 0° C.
  3. customquenched by addition of 5 ml of methanol dropwise
  4. stirringThe resulting white suspension was stirred for 20 min at 0° C.
  5. additionsat. aq. NaHCO3 (˜5 ml) was added
  6. additionfollowed by addition of 25% aq. ammonia (˜15 ml)
  7. stirringThe mixture was stirred for 30 min
  8. customDCM was removed in a stream of nitrogen
  9. additionThe mixture was diluted with water (10 ml) and 25% ammonia (10 ml)
  10. filtrationfiltered
  11. washThe white solid was washed with water twice
  12. customdried for 3 hrs on air

Sources & evidence

ORD record
ord-e4d9d1b1fa2949f897da2b35afeeb050
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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