Dimethylformamide → 4-(3-Fluoro-5-nitro-phenylsulfanyl)-1-methyl-piperidine

HRID 1822015Notes

Reaction equation

HRID 1822015 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([SH:8])[CH2:4][CH2:3]1.CN(C)C=O.[H-].[Na+].[F:16][C:17]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[C:19](F)[CH:18]=1>O>[F:16][C:17]1[CH:18]=[C:19]([S:8][CH:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[CH:20]=[C:21]([N+:23]([O-:25])=[O:24])[CH:22]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 752721,3-Difluoro-5-nitrobenzeneHCID 141803911-Methylpiperidine-4-thiol

Product 1

HCID 578936894-(3-Fluoro-5-nitro-phenylsulfanyl)-1-methyl-piperidineYield 11%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Combine 1-methyl-piperidine-4-thiol (1.4 g, 10.67 mmol) and N,N-dimethylformamide (10 mL) and cool to 0° C. Add 95% sodium hydride (0.28 g, 11.20 mmol), warm to ambient temperature and stir. After 40 min., add 1,3-difluoro-5-nitro-benzene (1.21 mL, 10.67 mmol), stir and heat at 65° C. After 3 hr., cool to ambient temperature and add water (50 mL). Extract with ethyl acetate (3×50 mL), wash combined organic layers with water (3×50 mL), aqueous NaCl solution (50 mL), dry organic layer over sodium sulfate, filter and concentrate. Purify residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride to obtain the title compound (0.31 g, 11%). Mass spectrum (electrospray): m/z=271.1 (M+1).

Workup

  1. stirringstir
  2. temperatureheat at 65° C
  3. waitAfter 3 hr
  4. temperature, cool to ambient temperature
  5. extractionExtract with ethyl acetate (3×50 mL)
  6. washwash
  7. filtrationfilter
  8. concentrationconcentrate
  9. washPurify residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride

Sources & evidence

ORD record
ord-464510ff0b1645e7a875868f4ecd30e9
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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