Potassium Phosphate, Tribasic → (S)-5-amino-2'-(5,6-dihydro-2H-pyran-3-yl)-4'-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-7'-ol

HRID 455718Notes

Reaction equation

HRID 455718 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[NH2:9][C:10]1[CH2:31][O:30][CH2:29][C@:12]2([C:25]3[CH:24]=[C:23](Br)[CH:22]=[C:21]([F:27])[C:20]=3[O:19][C:18]3[C:13]2=[CH:14][C:15]([OH:28])=[CH:16][CH:17]=3)[N:11]=1.[O:32]1[CH2:37][CH2:36][CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH2:33]1>O1CCOCC1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[NH2:9][C:10]1[CH2:31][O:30][CH2:29][C@:12]2([C:25]3[CH:24]=[C:23]([C:34]4[CH2:33][O:32][CH2:37][CH2:36][CH:35]=4)[CH:22]=[C:21]([F:27])[C:20]=3[O:19][C:18]3[C:13]2=[CH:14][C:15]([OH:28])=[CH:16][CH:17]=3)[N:11]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 158366332-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 67437656(S)-5-amino-2'-bromo-4'-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-7'-ol

Product 1

HCID 67438367(S)-5-amino-2'-(5,6-dihydro-2H-pyran-3-yl)-4'-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-7'-ol

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave vial, the potassium phosphate (1.014 g, 4.78 mmol), PdCl2(AmPhos)2 (0.085 g, 0.119 mmol), (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.604 g, 1.593 mmol), and 2-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.485 g, 2.310 mmol) were suspended in dioxane (6.5 mL) and water (2.5 mL). Argon gas was blown through the vessel, which was sealed and heated by microwave at 120° C. for 30 min. The mixture was concentrated. The residue was neutralized with half-saturated aqueous NH4Cl (35 mL). The aqueous phase was extracted with 5% MeOH/DCM (3×35 mL). The organics were combined, washed with dilute brine (15 mL), dried over sodium sulfate and concentrated to afford crude (S)-5-amino-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol which was used directly in the next step.

Workup

  1. customwas sealed
  2. concentrationThe mixture was concentrated
  3. extractionThe aqueous phase was extracted with 5% MeOH/DCM (3×35 mL)
  4. washwashed with dilute brine (15 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-180d19445e584931af9663249e61bf5c
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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