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

HRID 455656Notes

Reaction equation

HRID 455656 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][CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH2:34][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:35]4[CH2:36][CH2:37][O:32][CH2:33][CH:34]=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 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 67437656(S)-5-amino-2'-bromo-4'-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-7'-ol

Product 1

HCID 67438060(S)-5-amino-2'-(3,6-dihydro-2H-pyran-4-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, potassium phosphate (0.307 g, 1.448 mmol), PdCl2(AmPhos)2 (0.026 g, 0.036 mmol), (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.183 g, 0.483 mmol), and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.147 g, 0.700 mmol) were suspended in dioxane (4 mL) and water (1.6 mL). Argon was blown through the vessel, which was sealed and heated by microwave at 120° C. for 30 min. The reaction was concentrated, and the residue was neutralized with ⅓ saturated aqueous NH4Cl (15 mL) and the aqueous phase was extracted with 5% MeOH-DCM (3×25 mL). The organics were combined, washed with dilute brine (7 mL), and concentrated to afford (S)-5-amino-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol which was used in the next step without further purification.

Workup

  1. customwas sealed
  2. concentrationThe reaction was concentrated
  3. extractionthe aqueous phase was extracted with 5% MeOH-DCM (3×25 mL)
  4. washwashed with dilute brine (7 mL)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-59be17e2e5254e36ace2b20516289bb4
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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