Boron trifluoride etherate → 4-(4-Chlorobenzylthio)-4-(2-fluorophenyl)-1-methylpiperidine hydrochloride

HRID 1248501Notes

Reaction equation

HRID 1248501 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][SH:7])=[CH:4][CH:3]=1.B(F)(F)F.CCOCC.[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1(O)[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]1>C(O)(=O)C>[ClH:1].[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][S:7][C:26]2([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[F:19])[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 804094-Chlorobenzyl mercaptanHCID 126940234-(2-Fluorophenyl)-1-methylpiperidin-4-OL

Product 1

HCID 126940504-(4-Chlorobenzylthio)-4-(2-fluorophenyl)-1-methylpiperidine hydrochloride

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

9.9 ml (11.9 g) of 4-chlorobenzyl mercaptan and 11.1 ml of boron trifluoride etherate are added sequentially to 5.00 g of 4-(2-fluorophenyl)-4-hydroxy-1-methylpiperidine. Example 1a, in 11.1 ml of glacial acetic acid. The reaction is stirred at 55°-60° C. for 48 hours. The excess reagents are removed at 80° C. in vacuo and the residue is taken up with a 1:1 ether-2N hydrochloride acid mixture. This biphasic mixture is stirred for 2.5 hours and then for an additional ten minutes after 50 ml of ice are added. The ether layer is decanted off. The aqueous layer is sequentially washed with ether and filtered to collect a crude product. The product is washed with a small portion of water and then a large portion of ether to give a white powder. The powder is recrystallized from acetone to give white crystals, mp 164°-166° C. of 4-(4-chlorobenzylthio)-4-(2-fluorophenyl)-1 -methylpiperidine hydrochloride.

Workup

  1. customThe excess reagents are removed at 80° C. in vacuo
  2. stirringThis biphasic mixture is stirred for 2.5 hours
  3. additionfor an additional ten minutes after 50 ml of ice are added
  4. customThe ether layer is decanted off
  5. washThe aqueous layer is sequentially washed with ether
  6. filtrationfiltered
  7. customto collect a crude product
  8. washThe product is washed with a small portion of water
  9. customa large portion of ether to give a white powder
  10. customThe powder is recrystallized from acetone

Sources & evidence

ORD record
ord-c292458581b542518548cd0c5f018e76
Source dataset
uspto-grants-1985_06
Patent number
US04524207

Reaction notes

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