1-Chloro-4-(chloromethyl)benzene → HCID 59371348, compound

HRID 2095443Notes

Reaction equation

HRID 2095443 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Cl)=[CH:22][CH:21]=1.[NH4+].[Cl-]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][CH2:24][C:23]2[CH:26]=[CH:27][C:20]([Cl:19])=[CH:21][CH:22]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Product 1

HCID 59371348HCID 59371348, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(tert-butoxycarbonyl)-4-(2-hydroxyethyl)piperidine (708 mg, 3.09 mmol) in anhydrous THF (15 mL) was cooled to 0° C., and NaH (60% dispersion in oil, 148 mg, 3.7 mmol, 1.2 equiv.) was added all at once. Alkoxide formation was effected by stirring at room temperature for 2 h under N2, then 4-chlorobenzyl chloride (597 mg, 3.7 mmol, 1.2 equiv.) and tetra-n-butylammonium iodide (114 mg, 0.31 mmol, 0.1 equiv.) were added. The mixture was stirred at room temperature for 20 h. Saturated aqueous NH4Cl solution was added, and the product was extracted into EtOAc. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by CC (SiO2, hexane/EtOAc 4:1) to afford, after evaporation, 1-(tert-butoxycarbonyl)-4-[2-(4-chlorobenzyloxy)ethyl]piperidine (974 mg, 89%) as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.30 (d, 2H, J=8.4 Hz), 7.24 (d, 2H, J=6.8 Hz), 4.45 (s, 2H), 4.05 (d, 2H, J=13.2 Hz), 3.49 (t, 2H, J=6.0 Hz), 2.67 (t, 2H, J=12.8 Hz), 1.63 (d, 2H, J=13.6 Hz), 1.55 (m, 3H), 1.44 (s, 9H), 1.11 (m, 2H).

Workup

  1. stirringThe mixture was stirred at room temperature for 20 h
  2. extractionthe product was extracted into EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by CC (SiO2, hexane/EtOAc 4:1)
  6. customto afford
  7. customafter evaporation, 1-(tert-butoxycarbonyl)-4-[2-(4-chlorobenzyloxy)ethyl]piperidine (974 mg, 89%) as a pale yellow oil

Sources & evidence

ORD record
ord-9fbb0203369747179bcc09ebb7f4ee42
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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