Dimethylformamide → 4-(Isocyano(tosyl)methyl)-1-tosylpiperidine

HRID 1616343Notes

Reaction equation

HRID 1616343 reaction equation
[H-].[Na+].[C:3]1(C)[C:4]([S:9]([CH2:12][N+:13]#[C-:14])(=[O:11])=[O:10])=[CH:5][CH:6]=[CH:7][CH:8]=1.Br[CH:17]1[CH2:22][CH2:21][N:20]([S:23]([C:26]2[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH2:19][CH2:18]1.[CH3:33]N(C=O)C>C(OCC)(=O)C.[Li+].[Cl-]>[N+:13]([CH:12]([S:9]([C:4]1[CH:3]=[CH:8][C:7]([CH3:33])=[CH:6][CH:5]=1)(=[O:10])=[O:11])[CH:17]1[CH2:22][CH2:21][N:20]([S:23]([C:26]2[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH2:19][CH2:18]1)#[C-:14]

Participants

7

Reactant 4

HCID 6228Dimethylformamide3×HCID 24758Sodium hydrideHCID 113590324-Bromo-1-tosylpiperidineHCID 53627694Toluenesulfonylmethyl isocyanide

Product 1

HCID 595655894-(Isocyano(tosyl)methyl)-1-tosylpiperidine

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 433294Lithium ChlorideSolvent

Procedure

NaH (0.92 g, 23.07 mmol, 60% dispersion in oil) was added to DMF (70 mL) in one portion at 0° C. Toluenesulphonylmethyl isocyanide (3.0 g, 15.38 mmol) in DMF (12 mL) was added dropwise over 5 minutes and the mixture was stirred while warming to r.t. for 20 minutes. 4-Bromo-1-tosylpiperidine (4.46 g, 18.4 mmol) in DMF (10 mL) was then added dropwise over 3 minutes and the resulting mixture was stirred at r.t. for 16 h. The mixture was then diluted with ethyl acetate (250 mL) and LiCl (1 M aqueous solution, 60 mL), and the separated organic layer was washed with water (60 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (20% EtOAc/hexane) to provide 4-(isocyano(tosyl)methyl)-1-tosylpiperidine as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J=8.0 Hz, 2H), 7.61 (d, J=7.6 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.32 (d, J=7.6 Hz, 2H), 4.34 (d, J=4.0 Hz, 1H), 3.87-3.84 (m, 2H), 2.44 (s, 3H), 2.43 (s, 3H), 2.30-2.10 (m, 2H), 2.10-2.0 (m, 1H), 2.0-1.70 (m, 4H); MS (ESI) 451.1 (M+H+H2O)+.

Workup

  1. stirringthe resulting mixture was stirred at r.t. for 16 h
  2. washthe separated organic layer was washed with water (60 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (20% EtOAc/hexane)

Sources & evidence

ORD record
ord-920f63ab00e24992900f4b6506c972fc
Source dataset
uspto-grants-2014_07
Patent number
US08765788B2

Reaction notes

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