Potassium Acetate → 2-fluoro-7-(2-fluoropyridin-3-yl)-3-(trimethylsilyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 335824Notes

Reaction equation

HRID 335824 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](=[N:10][C:11]([F:25])=[C:12]([Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:13]=3)[O:8][C:5]2=[CH:6][CH:7]=1.[F:26][C:27]1[C:32](B(O)O)=[CH:31][CH:30]=[CH:29][N:28]=1.C([O-])(=O)C.[K+]>C(O)C.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:25][C:11]1[N:10]=[C:9]2[O:8][C:5]3[C:4]([C:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:14]2=[CH:13][C:12]=1[Si:21]([CH3:24])([CH3:23])[CH3:22])=[CH:3][C:2]([C:32]1[C:27]([F:26])=[N:28][CH:29]=[CH:30][CH:31]=1)=[CH:7][CH:6]=3

Participants

7

Reactant 3

HCID 517044Potassium AcetateHCID 27832702-Fluoropyridine-3-boronic acidHCID 58466199HCID 58466199, compound

Product 1

HCID 673835332-fluoro-7-(2-fluoropyridin-3-yl)-3-(trimethylsilyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

7-Bromo-2-fluoro-3-(trimethylsilyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.137 g, 0.324 mmol), bis-(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(ii) (0.011 g, 0.016 mmol), 2-fluoropyridin-3-ylboronic acid (0.055 g, 0.389 mmol), and potassium acetate (0.127 g, 1.298 mmol) were suspended in a mixture of ethanol (30 mL) and water (5 mL) and heated to 80° C. After 20 minutes the solution was cooled to rt and concentrated under reduced pressure to ˜10 mL. This solution was then diluted with water (100 mL) and EtOAc (100 mL). The phases were mixed and separated and the organics were dried with magnesium sulfate before filtered and evaporated to dryness under reduced pressure. Purification using silica chromatography (0-10% methanol in DCM gradient followed by a second column using dichloromethane to EtOAc gradient) gave the desired 2-fluoro-7-(2-fluoropyridin-3-yl)-3-(trimethylsilyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine

Workup

  1. temperatureAfter 20 minutes the solution was cooled to rt
  2. concentrationconcentrated under reduced pressure to ˜10 mL
  3. additionThis solution was then diluted with water (100 mL) and EtOAc (100 mL)
  4. additionThe phases were mixed
  5. customseparated
  6. dry with materialthe organics were dried with magnesium sulfate
  7. filtrationbefore filtered
  8. customevaporated to dryness under reduced pressure
  9. customPurification

Sources & evidence

ORD record
ord-bb0842e56e794a4b8fb470ac6b77be19
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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