1-Bromo-4-fluorobenzene → 1-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(4-fluorophenyl)-4-hydroxypiperidine

HRID 434404Notes

Reaction equation

HRID 434404 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.[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-].[NH4+]>BrC(Br)C.CCOCC.O1CCCC1>[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]([C:3]4[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=4)([OH:27])[CH2:25][CH2:26]3)=[N:16][O:17][C:13]=2[CH:12]=1

Participants

8

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 132078191-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-piperidone

Product 1

HCID 132078221-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(4-fluorophenyl)-4-hydroxypiperidineYield 54%

Reagents, catalysts & solvents 3

HCID 112011,1-DibromoethaneCatalystHCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 1.1 g of magnesium shavings and a few drops of dibromoethane in 30 ml of ether was added a solution of 7.9 g of p-bromofluorobenzene in 20 ml of ether at a rate to maintain reflux of the mixture. After the addition was complete, the mixture was slowly diluted with 30 ml of tetrahydrofuran and then a solution of 5 g of 1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-piperidone in 30 ml of tetrahydrofuran was slowly 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 recrystallized from hexanes/ether to give 3.6 g (54%) of product, mp 100°-101° C.

Workup

  1. temperatureto maintain
  2. temperaturereflux of the mixture
  3. additionAfter the addition
  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. customThe residue was recrystallized from hexanes/ether

Sources & evidence

ORD record
ord-971e61a003a8480681996ee90ff84b71
Source dataset
uspto-grants-1983_08
Patent number
US04396770

Reaction notes

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