1-Bromo-3-chlorobenzene → 4-(3-Chlorophenyl)-1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-hydroxypiperidine hydrochloride

HRID 434403Notes

Reaction equation

HRID 434403 reaction equation
[Mg].Br[C:3]1[CH:4]=[C:5]([Cl:9])[CH:6]=[CH:7][CH:8]=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>[ClH:9].[Cl:9][C:5]1[CH:4]=[C:3]([C:24]2([OH:27])[CH2:23][CH2:22][N:21]([CH2:20][CH2:19][CH2:18][C:15]3[C:14]4[CH:28]=[CH:29][C:11]([F:10])=[CH:12][C:13]=4[O:17][N:16]=3)[CH2:26][CH2:25]2)[CH:8]=[CH:7][CH:6]=1

Participants

8

Reactant 4

HCID 79281-Bromo-3-chlorobenzeneHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 132078191-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-piperidone

Product 1

HCID 132078214-(3-Chlorophenyl)-1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-hydroxypiperidine hydrochloride

Reagents, catalysts & solvents 3

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

Procedure

To a suspension of 1.2 g of magnesium shavings and a few drops of dibromoethane in 30 ml of ether was added a solution of 8.7 g of 3-bromochlorobenzene in 20 ml of ether at such a rate so as to maintain reflux. After the addition was complete, the mixture was diluted with 30 ml of tetrahydrofuran and then a solution of 6.3 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 to an oil. The oil was converted to 8.5 g (88%) of product, mp 170°-172° C., by treatment with ethereal hydrogen chloride. An analytical sample was obtained by recrystallization from ethyl acetate/methanol and had, mp 188°- 189° C.

Workup

  1. temperatureto maintain
  2. temperaturereflux
  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 to an oil
  9. customAn analytical sample was obtained by recrystallization from ethyl acetate/methanol

Sources & evidence

ORD record
ord-33b2dce5b70e4378aad32ac6c592989a
Source dataset
uspto-grants-1983_08
Patent number
US04396770

Reaction notes

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