Sodium Carbonate → HCID 58465947, compound

HRID 455714Notes

Reaction equation

HRID 455714 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.FC(F)(F)S(O[C:22]1[CH:35]=[C:34]2[C:25]([O:26][C:27]3[CH:28]=[CH:29][C:30]([C:49]4[C:50]([F:55])=[N:51][CH:52]=[CH:53][CH:54]=4)=[CH:31][C:32]=3[C@@:33]32[N:40]=[C:39]([NH:41]C(OC(C)(C)C)=O)CO[CH2:36]3)=[CH:24][CH:23]=1)(=O)=O.[C:58](=[O:61])([O-])[O-].[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:1]1[CH2:2][CH:3]=[C:4]([C:22]2[CH:35]=[CH:34][C:25]3[O:26][C:27]4[C:32](=[CH:31][C:30]([C:49]5[C:50]([F:55])=[N:51][CH:52]=[CH:53][CH:54]=5)=[CH:29][CH:28]=4)[C@:33]4([N:40]=[C:39]([NH2:41])[CH2:58][O:61][CH2:36]4)[C:24]=3[CH:23]=2)[CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 86658391HCID 86658391, compound

Product 1

HCID 58465947HCID 58465947, compoundYield 61.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

In a microwave vial, 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.062 g, 0.297 mmol), (S)-5-(tert-butoxycarbonylamino)-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.145 g, 0.238 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.027 g, 0.024 mmol) were taken up in DMF (3 mL). Aqueous sodium carbonate (1.0 M, 0.714 mL, 0.714 mmol) was added. Argon was blown through the vessel which was sealed and placed in an 85° C. oil bath. After 3 h, the reaction was concentrated. The residue was diluted with water (15 mL) and the aqueous phase was extracted with 3% MeOH/DCM (3×25 mL). The organics were combined, washed with brine (7 mL), dried over sodium sulfate and concentrated. The residue was transferred to a microwave vial with 3 mL of DCMm and tfa (0.275 mL, 3.57 mmol) was added. The vial was sealed and the reaction was stirred in a 65° C. oil bath for 2 h. The reaction was concentrated. The residue was neutralized with 0.5 M Na2CO3 (13 mL). The aqueous phase was extracted with 5% MeOH/DCM (3×25 mL). The organics were combined, washed with dilute brine (8 mL), dried over sodium sulfate and concentrated. The residue was purified by chromatography (7%-8% MeOH/DCM) to afford (R)-2′-(3,6-dihydro-2H-pyran-4-yl)-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (65 mg, 0.146 mmol).

Workup

  1. customwas sealed
  2. customplaced in an 85° C.
  3. concentrationthe reaction was concentrated
  4. additionThe residue was diluted with water (15 mL)
  5. extractionthe aqueous phase was extracted with 3% MeOH/DCM (3×25 mL)
  6. washwashed with brine (7 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. additionwas added
  10. customThe vial was sealed
  11. concentrationThe reaction was concentrated
  12. extractionThe aqueous phase was extracted with 5% MeOH/DCM (3×25 mL)
  13. washwashed with dilute brine (8 mL)
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated
  16. customThe residue was purified by chromatography (7%-8% MeOH/DCM)

Sources & evidence

ORD record
ord-994c86e2a7eb449f9a14368249a61f10
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

Loading…