Ammonium Chloride → HCID 14391479, compound

HRID 2073475Notes

Reaction equation

HRID 2073475 reaction equation
[Mg].Br[C:3]1[N:4]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])[CH:5]=[CH:6][CH:7]=1.[F:16][C:17]1[CH:35]=[CH:34][C:20]2[C:21]([CH2:24][CH2:25][CH2:26][N:27]3[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]3)=[N:22][O:23][C:19]=2[CH:18]=1.[NH4+].[Cl-]>O1CCCC1.CCOCC.BrC(Br)C>[F:16][C:17]1[CH:35]=[CH:34][C:20]2[C:21]([CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][C:30]([C:3]4[N:4]([CH2:8][C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=5[F:15])[CH:5]=[CH:6][CH:7]=4)([OH:33])[CH2:31][CH2:32]3)=[N:22][O:23][C:19]=2[CH:18]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 132078191-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-piperidoneHCID 14391470HCID 14391470, compound

Product 1

HCID 14391479HCID 14391479, compoundYield 72.3%

Reagents, catalysts & solvents 3

HCID 112011,1-DibromoethaneCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of magnesium turnings (1.0 g, 0.04 mole) in 25 ml tetrahydrofuran (THF) and 10 ml ether, was added a few drops of a solution of 2-bromo-1-(2-fluorobenzyl)pyrrole (10 g, 0.04 mole) in 30 ml THF. The reaction was initiated with a few drops of dibromoethane and heat, and reflux was maintained by the addition of the bromo compound. After stirring at reflux for 30 minutes, the mixture was cooled; then a solution of 1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-piperidone (5.2 g, 0.019 mole) in 50 ml THF was added. After stirring at ambient temperature for one hour, the mixture was poured into an NH4Cl solution, then extracted with ether. The ether layer was washed with water, then dried over anhydrous MgSO4. After evaporation of the solvent, the resultant oil (13 g), was purified by HPLC using ethyl acetate with 0.5% Diethylamine as the eluent to give 6.2 g of 1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-[1-(2-fluorobenzyl)pyrrol-2-yl]-4-piperidinol, m.p. 100°-4° C.

Workup

  1. temperatureheat
  2. temperaturereflux
  3. temperatureat reflux for 30 minutes
  4. temperaturethe mixture was cooled
  5. stirringAfter stirring at ambient temperature for one hour
  6. extractionextracted with ether
  7. washThe ether layer was washed with water
  8. dry with materialdried over anhydrous MgSO4
  9. customAfter evaporation of the solvent
  10. customthe resultant oil (13 g), was purified by HPLC

Sources & evidence

ORD record
ord-4f03912dde4e4defb47099a41ef6897e
Source dataset
uspto-grants-1990_04
Patent number
US04918069

Reaction notes

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