Triethylsilane → N-benzyloxycarbonyl-4-(4,5,6,7-tetrafluoroindol-3-yl)piperidine

HRID 843007Notes

Reaction equation

HRID 843007 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.[F:30][C:31]1[C:39]([F:40])=[C:38]([F:41])[C:37]([F:42])=[C:36]2[C:32]=1[CH:33]=[CH:34][NH:35]2.C([SiH](CC)CC)C>C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:33]2[C:32]3[C:36](=[C:37]([F:42])[C:38]([F:41])=[C:39]([F:40])[C:31]=3[F:30])[NH:35][CH:34]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 12052TriethylsilaneHCID 65367Trimethylsilyl triflateHCID 1400511H-Indole, 4,5,6,7-tetrafluoro-HCID 643496Benzyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 11395638N-benzyloxycarbonyl-4-(4,5,6,7-tetrafluoroindol-3-yl)piperidineYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-benzyloxycarbonyl-4-piperidone (20.2 g, 90.6 mmol) in methylene chloride (600 ml) at 0° C. was added trimethylsilyl trifluoromethanesulfonate (35.1 ml, 181.2 mmol) followed by the slow dropwise addition of a solution of 4,5,6,7-tetrafluoroindole (17.1 g, 90.6 mmol) in methylene chloride (300 ml) over 2.5 h. After 1.5 h, triethylsilane (57.9 ml, 362.4 mmol) was added and the reaction was allowed to warm to RT over 30 min. The reaction mixture was quenched with sat. sodium bicarbonate and the separated organic layer was dried over MgSO4 and concentrated in vacuo. The residue was partitioned between 50% acetonitrile/hexanes (1400 ml) and the separated acetonitrile layer was concentrated in vacuo. The solid residue was recrystallized from absolute EtOH to afford N-benzyloxycarbonyl-4-(4,5,6,7-tetrafluoroindol-3-yl)piperidine (66%) as a white solid.

Workup

  1. customThe reaction mixture was quenched with sat. sodium bicarbonate
  2. dry with materialthe separated organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between 50% acetonitrile/hexanes (1400 ml)
  5. concentrationthe separated acetonitrile layer was concentrated in vacuo
  6. customThe solid residue was recrystallized from absolute EtOH

Sources & evidence

ORD record
ord-20d90d9409dd477bb4ea60ad4e467e00
Source dataset
uspto-grants-2002_04
Patent number
US06376506B1

Reaction notes

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