Acetic Acid → 4-(2-Fluorobenzylthio)-4-(2-fluorophenyl)-1-methylpiperidine maleate

HRID 1248512Notes

Reaction equation

HRID 1248512 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([OH:15])[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1.[F:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][SH:20].B(F)(F)F.CC[O:31][CH2:32][CH3:33].[C:34]([OH:37])(=[O:36])[CH3:35]>>[C:32]([OH:31])(=[O:15])/[CH:33]=[CH:35]\[C:34]([OH:37])=[O:36].[F:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][S:20][C:8]1([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 8000Boron trifluoride etherateHCID 5221752-Fluorobenzyl mercaptanHCID 126940234-(2-Fluorophenyl)-1-methylpiperidin-4-OL

Product 1

HCID 126940404-(2-Fluorobenzylthio)-4-(2-fluorophenyl)-1-methylpiperidine maleate

Procedure

A mixture of 4-(2-fluorophenyl)-4-hydroxy-1-methylpiperidine of Example 1a (15.8 g), 12 ml of 2-fluorobenzyl mercaptan and 20 ml of boron trifluoride etherate in 15 ml of glacial acetic acid is stirred at 65°-70° C. for 16 hours. The excess reagents are removed under reduced pressure, the residue is triturated with 300 ml of 0.5N HCl and 100 ml of ether. After standing at 5°-10° C. for 30 minutes, a crystalline precipitate is filtered, air dried and made basic with 10% aqueous NH4OH. The liberated amine is taken up in ether, dried and concentrated to a yellowish oil which is then converted to its maleate in ether, recrystallization of the crude salt from methanol-ether gives colorless prisms, m.p. 153°-154° C. of 4-(2-fluorobenzylthio)-4-(2-fluorophenyl)-1-methylpiperidine maleate.

Workup

  1. customThe excess reagents are removed under reduced pressure
  2. customthe residue is triturated with 300 ml of 0.5N HCl and 100 ml of ether
  3. waitAfter standing at 5°-10° C. for 30 minutes
  4. filtrationa crystalline precipitate is filtered
  5. customair dried
  6. customdried
  7. concentrationconcentrated to a yellowish oil which
  8. customis then converted to its maleate in ether, recrystallization of the crude salt from methanol-ether

Sources & evidence

ORD record
ord-3e3c249d726546f1be4b4dc3421cc9a2
Source dataset
uspto-grants-1985_06
Patent number
US04524207

Reaction notes

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