Tetrahydrofuran → HCID 67242237, compound

HRID 1970318Notes

Reaction equation

HRID 1970318 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:21][CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.[N:27]1[CH:32]=[CH:31][CH:30]=[C:29](B(O)O)[CH:28]=1.C1COCC1.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.O.C(OCC)(=O)C>[CH2:22]([O:21][C:12]1[CH:13]=[C:14]2[C@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:29]4[CH:28]=[N:27][CH:32]=[CH:31][CH:30]=4)[CH:3]=3)[O:8][C:9]2=[CH:10][CH:11]=1)[C:23]([CH3:26])([CH3:25])[CH3:24]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 67240591HCID 67240591, compound

Product 1

HCID 67242237HCID 67242237, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Combined (R)-3-bromo-7-(neopentyloxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (9.15 g, 21.88 mmol), tetrakis(triphenylphosphine)palladium (2.53 g, 2.188 mmol) and 3-pyridylboronic acid (6.72 g, 54.7 mmol). Added THF (146 mL, 21.88 mmol) followed by potassium carbonate (1.5 M) (58.3 mL, 88 mmol). Flushed reaction tube with argon, sealed and heated at 110° C. for 2.5 hours. The reaction was allowed to cool to room temperature before being poured into a separatory funnel containing ethyl acetate (500 mL). Water (1000 mL) was added and, the layers were separated and the aqueous layer was extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown foam. This foam was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (330 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (R)-7-(neopentyloxy)-3-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a light yellow solid.

Workup

  1. customFlushed
  2. customreaction tube with argon
  3. customsealed
  4. temperatureto cool to room temperature
  5. additionbefore being poured into a separatory funnel
  6. customthe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×500 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto provide a brown foam
  13. customThis foam was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (330 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-0921e969a8a642fe916589e4bd7dcc4e
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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