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

HRID 1970304Notes

Reaction equation

HRID 1970304 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-olYield 89.2%

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), Pd(PPh3)4 (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. After stirring for 50 minutes, 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 chromatographed 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 (259.36 mg, 0.722 mmol, 89% yield) 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. customthe mixture was partitioned between brine and 10% iPrOH/EtOAc
  6. customThe layers were separated
  7. extractionthe aq. layer was extracted with EtOAc
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was chromatographed on an 80-g Redi-Sep column
  12. washeluting with 0-80% of a 90:10:1
  13. additionmix of DCM/MeOH/NH4OH in DCM

Sources & evidence

ORD record
ord-c169f37d328241989cb12e7bf46ec5a6
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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