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

HRID 335771Notes

Reaction equation

HRID 335771 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

Conditions

Temperature
100 °C

Procedure

A 350-mL pressure vessel was charged with (R)-2-amino-2′-bromo-5H-spiro[oxazole-4,9′-xanthen]-7′-ol (4.00 g, 11.52 mmol), 3-pyridylboronic acid (3.54 g, 28.8 mmol), tetrakis(triphenylphosphine)palladium(0) (1.331 g, 1.152 mmol), THF (57.6 mL), and potassium carbonate (2.0M aq. solution) (28.8 mL, 57.6 mmol). The vessel was sealed and heated to 100° C. and stirred for 2 hours. The layers were partitioned between EtOAc (20 mL) and water (20 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (emulsion!), dried over sodium sulfate and filtered with the aid of 10% MeOH/DCM. The filtrate was evaporated to give a yellow solid. This solid was taken up in minimal DCM and sonicated for 5 min. The solid was filtered and washed with DCM (30 mL). Filtering and washing with DCM afforded (S)-2-amino-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol as a pale-yellow solid

Workup

  1. customThe vessel was sealed
  2. customThe layers were partitioned between EtOAc (20 mL) and water (20 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  5. washThe combined organic layers were washed with brine (emulsion!)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered with the aid of 10% MeOH/DCM
  8. customThe filtrate was evaporated
  9. customto give a yellow solid
  10. customsonicated for 5 min
  11. filtrationThe solid was filtered
  12. washwashed with DCM (30 mL)
  13. filtrationFiltering
  14. washwashing with DCM

Sources & evidence

ORD record
ord-5ae4a884e88e45739bc45c974334c7b6
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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