Water → (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 455710Notes

Reaction equation

HRID 455710 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[O:9]1[CH2:14][CH2:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH2:10]1.[NH2:24][C:25]1[CH2:46][O:45][CH2:44][C@:27]2([C:40]3[CH:39]=[C:38](Br)[CH:37]=[C:36]([F:42])[C:35]=3[O:34][C:33]3[C:28]2=[CH:29][C:30]([OH:43])=[CH:31][CH:32]=3)[N:26]=1.O>O1CCOCC1.[NH4+].[Cl-].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>[NH2:24][C:25]1[CH2:46][O:45][CH2:44][C@:27]2([C:40]3[CH:39]=[C:38]([C:11]4[CH2:10][O:9][CH2:14][CH2:13][CH:12]=4)[CH:37]=[C:36]([F:42])[C:35]=3[O:34][C:33]3[C:28]2=[CH:29][C:30]([OH:43])=[CH:31][CH:32]=3)[N:26]=1

Participants

8

Reactant 4

HCID 962WaterHCID 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 25517Ammonium ChlorideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave vial, the potassium phosphate (0.771 g, 3.63 mmol), PdCl2(AmPhos)2 (0.064 g, 0.091 mmol) and 2-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.356 g, 1.695 mmol) were loaded. The (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.459 g, 1.211 mmol) was added as a solution in dioxane (6 mL). Water (2.4 mL) was added and argon gas was blown through the vessel, which was sealed and heated by microwave at 120° C. for 30 min. The residue was taken up in half-saturated aqueous NH4Cl (30 mL) and the aqueous phase was extracted with 5% MeOH/DCM (3×25 mL). The organics were combined, washed with brine (7 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. extractionthe aqueous phase was extracted with 5% MeOH/DCM (3×25 mL)
  3. washwashed with brine (7 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c8b074dc22774754992a91f73474752e
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

Loading…