Tetrahydrofuran → (S)-2-amino-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2'-ol

HRID 335866Notes

Reaction equation

HRID 335866 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:21]=1)[C:18]1[CH:17]=[C:16](Br)[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([OH:20])=[CH:9][CH:10]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.C1COCC1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.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>[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:21]=1)[C:6]1[CH:7]=[C:8]([OH:20])[CH:9]=[CH:10][C:11]=1[O:12][C:13]1[C:18]2=[CH:17][C:16]([C:24]2[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=2)=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 58466172(R)-2-amino-2'-bromo-5H-spiro[oxazole-4,9'-xanthen]-7'-ol

Product 1

HCID 58466221(S)-2-amino-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2'-ol

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

A 75-mL pressure vessel was charged with (R)-2-amino-2′-bromo-5H-spiro[oxazole-4,9′-xanthen]-7′-ol (3.25 g, 9.36 mmol), pyridin-3-ylboronic acid (2.88 g, 23.40 mmol), tetrakis(triphenylphosphine)palladium(0) (1.081 g, 0.936 mmol), THF (46.8 mL), and potassium carbonate (23.40 mL, 46.8 mmol) (as a 2.0 M aq. solution). The vessel was sealed and placed in a 100° C. oil bath for 6 hours. The mixture was partitioned between EtOAc (50 mL) and water (50 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2×30 mL. The combined mixture was dried over sodium sulfate and filtered with the aid of 10% MeOH/CH2Cl2. The filtrate was evaporated to give a yellow solid. This solid was taken up in CH2Cl2 (80 mL) and sonicated for 5 min. The solid was filtered and washed with CH2Cl2 (2×40 mL), then air-dried on the filter. The filtrate was evaporated and again taken up in CH2Cl2 (80 mL). The mixture was sonicated for 10 min, then filtered and washed with CH2Cl2 (30 mL). The solid was air-dried and combined with the first solid to give (S)-2-amino-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol. MS m/z=346.0 [M+H].

Workup

  1. customThe vessel was sealed
  2. customplaced in a 100° C.
  3. customfor 6 hours
  4. customThe mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×30 mL
  7. dry with materialThe combined mixture was dried over sodium sulfate
  8. filtrationfiltered with the aid of 10% MeOH/CH2Cl2
  9. customThe filtrate was evaporated
  10. customto give a yellow solid
  11. customsonicated for 5 min
  12. filtrationThe solid was filtered
  13. washwashed with CH2Cl2 (2×40 mL)
  14. customair-dried on the filter
  15. customThe filtrate was evaporated
  16. customThe mixture was sonicated for 10 min
  17. filtrationfiltered
  18. washwashed with CH2Cl2 (30 mL)
  19. customThe solid was air-dried

Sources & evidence

ORD record
ord-b51a5c169277437f9059a58959e5bf45
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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