Triethylamine → HCID 15462945, compound

HRID 397600Notes

Reaction equation

HRID 397600 reaction equation
[CH:1]1([C:4]([CH:6]([N:14]2[CH2:19][CH2:18][CH:17](O)[CH2:16][CH2:15]2)[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[F:13])=[O:5])[CH2:3][CH2:2]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[C:33]([O-:36])(=[S:35])[CH3:34].[K+]>ClCCl.O.CS(C)=O>[C:33]([S:35][CH:17]1[CH2:18][CH2:19][N:14]([CH:6]([C:4]([CH:1]2[CH2:3][CH2:2]2)=[O:5])[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[F:13])[CH2:15][CH2:16]1)(=[O:36])[CH3:34]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 15462959HCID 15462959, compoundHCID 23670855Potassium ethanethioate

Product 1

HCID 15462945HCID 15462945, compoundYield 37.1%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

8.0 g (28.9 mmol) of 1-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4-hydroxypiperidine were dissolved in 50 ml of dichloromethane, followed by the addition of 2.92 g (28.9 mmol) of triethylamine. A 10 ml dichloromethane solution of 3.31 g (28.9 mmol) of methanesulfonyl chloride was added dropwise under ice cooling and the resulting mixture was stirred at room temperature for 1 hour. The solvent was then distilled off under reduced pressure. Ethyl acetate was added to the residue and the triethylamine hydrochloride thus precipitated was filtered off. The filtrate was concentrated under reduced pressure, whereby crude 1-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4-methylsulfonyloxypiperidine was obtained. To the resulting crude product were added 50 ml of dimethyl sulfoxide (DMSO) and 19.8 g (170 mmol) of potassium thioacetate and the resulting mixture was stirred at 50° C. for 4 hours. Water was added to the reaction mixture. The resulting mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was subjected to chromatography on a silica gel column (eluting solvent: toluene/ethyl acetate=19/1), whereby a reddish brown oil was obtained. The oil was then crystallized from hexane, whereby 3.6 g of 4-acetylthio-1-(α-cyclopropylcarbonyl-2-fluorobenzyl)piperidine were obtained as pale brown crystals (yield: 37%).

Workup

  1. distillationThe solvent was then distilled off under reduced pressure
  2. additionEthyl acetate was added to the residue
  3. customthe triethylamine hydrochloride thus precipitated
  4. filtrationwas filtered off
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customwhereby crude 1-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4-methylsulfonyloxypiperidine was obtained
  7. stirringthe resulting mixture was stirred at 50° C. for 4 hours
  8. extractionThe resulting mixture was extracted with ethyl acetate
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationdistilled under reduced pressure
  11. customto remove the solvent
  12. washThe residue was subjected to chromatography on a silica gel column (eluting solvent: toluene/ethyl acetate=19/1), whereby a reddish brown oil
  13. customwas obtained
  14. customThe oil was then crystallized from hexane

Sources & evidence

ORD record
ord-10a2308a7586434ba2281b562213db1f
Source dataset
uspto-grants-2003_08
Patent number
US06610708B1

Reaction notes

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