Boron tribromide → (S)-5-amino-2'-bromo-4'-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-7'-ol
Reaction equation
[Br:1][C:2]1[CH:15]=[C:14]([F:16])[C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:17]C)=[CH:9][CH:10]=3)[C@:5]3([N:23]=[C:22]([NH2:24])[CH2:21][O:20][CH2:19]3)[C:4]=2[CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:24][C:22]1[CH2:21][O:20][CH2:19][C@:5]2([C:4]3[CH:3]=[C:2]([Br:1])[CH:15]=[C:14]([F:16])[C:13]=3[O:12][C:11]3[C:6]2=[CH:7][C:8]([OH:17])=[CH:9][CH:10]=3)[N:23]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
In a 500-mL flask, the (S)-2′-bromo-4′-fluoro-7′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.595 g, 1.513 mmol) was dissolved in DCM (45 mL). The orange solution was cooled to 0° C. and a DCM solution of boron tribromide (1.0 M, 4.54 mL, 4.54 mmol) was added. After 2 h, the reaction mixture was quenched with 20 mL of 9:1 NH4Cl/NH4OH. The mixture was diluted further with water (10 mL) and the aqueous phase was extracted with 5% MeOH-dcm (3×60 mL). The organics were combined, washed with brine (20 mL), dried over sodium sulfate and concentrated to afford crude (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.574 g, 1.21 mmol) which was used directly in the next step.
Workup
- customthe reaction mixture was quenched with 20 mL of 9:1 NH4Cl/NH4OH
- additionThe mixture was diluted further with water (10 mL)
- extractionthe aqueous phase was extracted with 5% MeOH-dcm (3×60 mL)
- washwashed with brine (20 mL)
- dry with materialdried over sodium sulfate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-6fef1c3743b14d2db905b56fd4e1180b
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08497264B2
Reaction notes
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