Sodium hydride → 6-(2-Methoxybenzyl)-8-phenyl-1,6-diazabicyclo[3.2.1]octane

HRID 1459278Notes

Reaction equation

HRID 1459278 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:24]=[CH:23][CH:22]=[CH:21][C:6]=1[CH2:7][NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][NH:11][C@H:10]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl[CH2:26]OCC1C=CC=CC=1>O1CCCC1>[CH3:3][O:4][C:5]1[CH:24]=[CH:23][CH:22]=[CH:21][C:6]=1[CH2:7][N:8]1[CH2:26][N:11]2[CH:10]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:9]1[CH2:14][CH2:13][CH2:12]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 137983Benzyl chloromethyl etherHCID 5311057CP-99994

Product 1

HCID 186867896-(2-Methoxybenzyl)-8-phenyl-1,6-diazabicyclo[3.2.1]octane

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (1.47 g, 36.8 mmol of a 60% dispersion in oil) was added to a round-bottomed flask fitted with an N2 inlet, condensor, stirrer and washed with hexane to remove the oil. Anhydrous tetrahydrofuran (THF), 50 mL, was added followed by 6.30 grams (18.9 mmol) of (2S, 3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine in 50 mL of tetrahydrofuran. After heating to reflux for two hours, the mixture was allowed to cool to room temperature and was treated dropwise with benzyl chloromethyl ether (5.1 mL, 36.8 mmol). The mixture was stirred overnight and the excess sodium hydride quenched with water. After being stirred an additional hour, the organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layers were combined and washed with saturated aqueous sodium chloride before drying over magnesium sulfate. Concentration in vacuo gave a solid which recrystallized from methanol/methylene chloride to a white solid, 2.36 grams (40%), mp 105°-107° C. Mass Spectrum (m/e): 309 (M+1, 100%), 159 (12%). 1H-NMR (CDCl3) δ1.45-2.20 (m, 5H), 3.15 (m, 2H), 3.5 (d, 1H), 3.65-3.85 (m, 2H), 3.75 (s, 3H), 3.95 (d, 1H), 4.10 (d, 1H), 6.8 (d, 1H), 6.95 (t, 1H), 7.15-7.6 (m, 7H). Anal. Calc'd for C20 H24N2O: C, 77.88; H, 7.83, N, 9.08. Found: C, 77.72; H, 7.75; N, 9.04.

Workup

  1. customfitted with an N2 inlet
  2. washcondensor, stirrer and washed with hexane
  3. customto remove the oil
  4. additionAnhydrous tetrahydrofuran (THF), 50 mL, was added
  5. temperatureAfter heating
  6. temperatureto reflux for two hours
  7. customthe excess sodium hydride quenched with water
  8. stirringAfter being stirred an additional hour
  9. customthe organic layer was separated
  10. extractionthe aqueous layer was extracted with methylene chloride
  11. washwashed with saturated aqueous sodium chloride
  12. dry with materialbefore drying over magnesium sulfate
  13. concentrationConcentration in vacuo
  14. customgave a solid which
  15. customrecrystallized from methanol/methylene chloride to a white solid, 2.36 grams (40%), mp 105°-107° C

Sources & evidence

ORD record
ord-be3293bd165947f3b34efe8dbaff277b
Source dataset
uspto-grants-1998_12
Patent number
US05854239

Reaction notes

Loading…