Potassium Carbonate → (S)-2'-amino-3-p-tolyl-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

HRID 335748Notes

Reaction equation

HRID 335748 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17](Br)[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([OH:21])=[CH:10][CH:11]=3)[N:6]=1.B(O)(O)[C:23]1[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>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([C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:23]4[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=4)[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([OH:21])=[CH:10][CH:11]=3)[N:6]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 79799Tolylboronic acidHCID 58466114(S)-2'-amino-3-bromo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

Product 1

HCID 67240012(S)-2'-amino-3-p-tolyl-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A vial was charged (S)-2′-amino-3-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol (282 mg, 0.809 mmol), p-tolylboronic acid (220 mg, 1.618 mmol), potassium carbonate (559 mg, 4.04 mmol), tetrakis(triphenylphosphine)palladium (46.7 mg, 0.040 mmol). The vial was flushed with Ar (g), then Dioxane (4044 μL) and water (2 mL) were added in sequence. The vial was sealed and placed in an 80° C. oil bath for 1 hour. The mixture was partitioned between brine and 10% iPrOH/EtOAc. The layers were separated, and the aq. layer was extracted with EtOAc. The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was chomatographed on an 80-g Redi-Sep column, eluting with 0-80% of a 90:10:1 mix of DCM/MeOH/NH4OH in DCM to give (S)-2′-amino-3-p-tolyl-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol as an orange solid.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additionDioxane (4044 μL) and water (2 mL) were added in sequence
  3. customThe vial was sealed
  4. customplaced in an 80° C.
  5. customfor 1 hour
  6. customThe mixture was partitioned between brine and 10% iPrOH/EtOAc
  7. customThe layers were separated
  8. extractionthe aq. layer was extracted with EtOAc
  9. dry with materialThe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. washeluting with 0-80% of a 90:10:1
  13. additionmix of DCM/MeOH/NH4OH in DCM

Sources & evidence

ORD record
ord-8d77a5746bf343efbcc0594c26abe08d
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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