Dichloromethane → 5-Fluorospiro[indoline-3,3'-piperidin]-2-one hydrochloride

HRID 1835843Notes

Reaction equation

HRID 1835843 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(OC(C)(C)C)=O)[CH2:15][CH2:16][CH:17]=1)=[O:11].BrC1C=C(F)C=CC=1N.C[Al](C)C.COC(C1CN(C(OC(C)(C)C)=O)CCC=1)=O.C([O-])(O)=O.[Na+].[Cl:60]CCl>>[ClH:60].[F:8][C:6]1[CH:5]=[C:4]2[C:12]3([CH2:17][CH2:16][CH2:15][NH:14][CH2:13]3)[C:10](=[O:11])[NH:9][C:3]2=[CH:2][CH:7]=1

Participants

7

Reactant 6

HCID 6344Dichloromethane3×HCID 2428732-Bromo-4-fluoroanilineHCID 516892Sodium BicarbonateHCID 111284441-Tert-butyl 3-methyl 1,2,5,6-tetrahydropyridine-1,3-dicarboxylateHCID 12991542HCID 12991542, compoundHCID 16682925Trimethylaluminum

Product 1

HCID 235007175-Fluorospiro[indoline-3,3'-piperidin]-2-one hydrochlorideYield 86%

Procedure

t-Butyl 3-(2-bromo-4-fluorophenylcarbamoyl)-1,2,5,6-tetrahydropyridine-1-carboxylate. 2-Bromo-4-fluoroaniline (2.53 g, 13.3 mmol) was dissolved in dichloromethane (30 mL) under N2-atmosphere and trimethylaluminium (2.0 M in hexanes, 8 mL) was added. The solution was stirred during 15 minutes, whereupon a solution of 5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-t-butyl ester 3-methyl ester (3.67 g, 13.3 mmol) in DCM (20 mL) was added. The mixture was refluxed overnight and saturated NaHCO3 was carefully added followed by DCM. The aqueous phase was extracted with DCM. The crude product was purified by chromatography on silica gel using a gradient of toluene to acetonitrile to give the title compound (4.55 g) in 86% yield as an yellow oil. Rf 0.54 (toluene/acetonitrile 3:1). MS(TSP+) m/z calcd for [M+NH4]+: 416, 418, observed: 416, 418.

Workup

  1. additionwas added
  2. temperatureThe mixture was refluxed overnight
  3. extractionThe aqueous phase was extracted with DCM
  4. customThe crude product was purified by chromatography on silica gel using a gradient of toluene to acetonitrile

Sources & evidence

ORD record
ord-17899bd98f8d44089ef2f902cec4be9b
Source dataset
uspto-grants-2004_08
Patent number
US06774132B1

Reaction notes

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