Water → HCID 67437751, compound

HRID 455713Notes

Reaction equation

HRID 455713 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[C:15](B(O)O)=[CH:14][CH:13]=[CH:12][N:11]=1.[NH2:19][C:20]1[CH2:40][O:39][CH2:38][C@@:22]2([C:35]3[CH:34]=[C:33](Br)[CH:32]=[CH:31][C:30]=3[O:29][C:28]3[C:23]2=[CH:24][C:25]([OH:37])=[CH:26][CH:27]=3)[N:21]=1.O>O1CCOCC1>[NH2:19][C:20]1[CH2:40][O:39][CH2:38][C@@:22]2([C:35]3[CH:34]=[C:33]([C:15]4[C:10]([F:9])=[N:11][CH:12]=[CH:13][CH:14]=4)[CH:32]=[CH:31][C:30]=3[O:29][C:28]3[C:23]2=[CH:24][C:25]([OH:37])=[CH:26][CH:27]=3)[N:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 67436986HCID 67436986, compound

Product 1

HCID 67437751HCID 67437751, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a microwave vial, potassium phosphate (0.615 g, 2.90 mmol), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (0.068 g, 0.097 mmol), 2-fluoropyridin-3-ylboronic acid (0.170 g, 1.208 mmol) and (R)-5-amino-2′-bromo-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.349 g, 0.966 mmol) were suspended in dioxane (8 mL). Water (2 mL) was added, and argon gas was blown through the vessel, which was then sealed and heated in a 100° C. oil bath for 3 h. The reaction was concentrated to remove the dioxane. The residue was diluted with aqueous NH4Cl (15 mL) and the aqueous phase was extracted with 5% MeOH/DCM (3×33 mL). The organics were combined, washed with dilute brine (8 mL), dried over sodium sulfate and concentrated to afford crude (S)-5-amino-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol which was used directly in the next step.

Workup

  1. customwas then sealed
  2. concentrationThe reaction was concentrated
  3. customto remove the dioxane
  4. additionThe residue was diluted with aqueous NH4Cl (15 mL)
  5. extractionthe aqueous phase was extracted with 5% MeOH/DCM (3×33 mL)
  6. washwashed with dilute brine (8 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-bcdf94fc96684b24836a41b9b6c9696d
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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