Triethylamine → HCID 15462960, compound

HRID 2288024Notes

Reaction equation

HRID 2288024 reaction equation
[CH:1]1([C:4]([CH:6]([N:14]2[CH2:19][CH2:18][CH:17]([OH:20])[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.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>ClCCl>[CH:1]1([C:4]([CH:6]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][S:29]([CH3:28])(=[O:31])=[O:30])[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

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 15462959HCID 15462959, compound

Product 1

HCID 15462960HCID 15462960, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. additionEthyl acetate was added to the residue and triethylamine hydrochloride
  3. customso precipitated
  4. filtrationwas filtered off
  5. concentrationThe filtrate was concentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-8d7b8415b9584c94bf7de62b42a7b278
Source dataset
uspto-grants-2000_07
Patent number
US06087379

Reaction notes

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