p-Xylyl bromide → HCID 59371717, compound

HRID 2095452Notes

Reaction equation

HRID 2095452 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+].[CH3:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Br)=[CH:22][CH:21]=1.[NH4+].[Cl-]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][CH2:19][C:20]2[CH:27]=[CH:26][C:23]([CH3:24])=[CH:22][CH:21]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 7721p-Xylyl bromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Product 1

HCID 59371717HCID 59371717, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(tert-butoxycarbonyl)-4-(2-hydroxyethyl)piperidine (328 mg, 1.43 mmol) in anhydrous THF (10 mL) was cooled to 0° C., and NaH (60% dispersion in oil, 69 mg, 1.71 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-methylbenzyl bromide (317 mg, 1.71 mmol, 1.2 equiv.) was added. The mixture was stirred at room temperature overnight. 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, EtOAc/hexane 1:4) to afford 1-(tert-butoxycarbonyl)-4-[2-(4-methylbenzyloxy)ethyl]piperidine (470 mg, 99%) after evaporation. 1H NMR (CDCl3, 400 MHz) δ 7.21 (d, 2H, J=8.0 Hz), 7.14 (d, 2H, J=8.0 Hz), 4.45 (s, 2H), 4.04 (d, 2H, J=13.6 Hz), 3.48 (t, 2H, J=6.4 Hz), 2.66 (t, 2H, J=13.6 Hz), 2.32 (s, 3H), 1.60 (m, 2H), 1.54 (m, 3H), 1.44 (s, 9H), 1.10(m, 2H).

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  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, EtOAc/hexane 1:4)

Sources & evidence

ORD record
ord-6f3f475b615540d198c595de11e14676
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

Loading…