Triethylamine → HCID 68762264, compound

HRID 2190027Notes

Reaction equation

HRID 2190027 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([C:12]1[CH2:13][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15][CH2:16][CH:17]=1)=[O:11].CCN(CC)CC>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:8][C:6]1[CH:7]=[C:2]2[C:12]3([CH2:17][CH:16]=[CH:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[C:10](=[O:11])[NH:9][C:3]2=[CH:4][CH:5]=1

Participants

6

Reactant 2

HCID 8471TriethylamineHCID 12991542HCID 12991542, compound

Product 1

HCID 68762264HCID 68762264, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of tert-butyl 3-(2-bromo-4-fluorophenylcarbamoyl)-5,6-dihydropyridine-1(2H)-carboxylate (1.30 g, 3.56 mmol) in DMF (18 mL) under N2 was added successively Et3N (1.13 mL, 8.14 mmol), tetrabutylammonium bromide (1.26 g, 3.91 mmol) and Pd(OAc)2 (0.146 g, 0.651 mmol). The resulting mixture was heated at about 100° C. for 3 h. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with 1N HCl and brine, dried and concentrated. The residue was purified by column chromatography (hexanes:EtOAc, 4:1) to give tert-butyl 5-fluoro-2-oxo-2′,4′-dihydro-1′H-spiro[indoline-3,3′-pyridine]-1′-carboxylate (0.80 g, 77%). LCMS (APCI+) m/z 219 [M+H-Boc]+; Rt=3.41 min.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between EtOAc and water
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washThe combined organic layers were washed with 1N HCl and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (hexanes:EtOAc, 4:1)

Sources & evidence

ORD record
ord-dea514931814481c97246c1dc00f67db
Source dataset
uspto-grants-2012_12
Patent number
US08324221B2

Reaction notes

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