2-Bromotoluene → 1-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-hydroxy-4-(2-methylphenyl)piperidine hydrochloride

HRID 1649139Notes

Reaction equation

HRID 1649139 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH3:9].[F:10][C:11]1[CH:29]=[CH:28][C:14]2[C:15]([CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]3)=[N:16][O:17][C:13]=2[CH:12]=1.[Cl-:30].[NH4+]>BrC(Br)C.CCOCC.O1CCCC1>[ClH:30].[F:10][C:11]1[CH:29]=[CH:28][C:14]2[C:15]([CH2:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][C:24]([OH:27])([C:3]4[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=4[CH3:9])[CH2:25][CH2:26]3)=[N:16][O:17][C:13]=2[CH:12]=1

Participants

8

Reactant 4

HCID 72362-BromotolueneHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 132078191-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-piperidone

Product 1

HCID 132078241-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-hydroxy-4-(2-methylphenyl)piperidine hydrochloride

Reagents, catalysts & solvents 3

HCID 112011,1-DibromoethaneCatalystHCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 0.9 g of magnesium shavings and a few drops of dibromoethane in 30 ml of ether was added a solution of 6.2 g of 2-bromotoluene in 30 ml of ether. After the addition was complete, the mixture was stirred under reflux for one hr, cooled, and a solution of 5 g of 1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-piperidone in 50 ml of tetrahydrofuran was added. After one hr, the mixture was diluted with ether, poured into 400 ml of saturated ammonium chloride solution and extracted with ether. The organic extracts were washed with water (2×), saturated sodium chloride solution and dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was converted to 6.4 g (82%) of product by treatment with ethereal hydrogen chloride. Recrystallization from ethyl acetate/methanol gave the analytical sample, mp 191°-192° C. (dec).

Workup

  1. additionAfter the addition
  2. temperatureunder reflux for one hr
  3. temperaturecooled
  4. extractionextracted with ether
  5. washThe organic extracts were washed with water (2×), saturated sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customRecrystallization from ethyl acetate/methanol
  10. customgave the analytical sample, mp 191°-192° C. (dec)

Sources & evidence

ORD record
ord-b81c69d200334ce8a4a6e43853f2ea09
Source dataset
uspto-grants-1983_11
Patent number
US04415581

Reaction notes

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