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

HRID 1872508ノート

反応式

HRID 1872508 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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, condenser, 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)δ 1.45-2.20 (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 C20H24N2O; C, 77.88; H, 7.83, N, 9.08. Found: C, 77.72; H, 7.75; N, 9.04.

後処理

  1. customfitted with an N2 inlet, condenser, stirrer
  2. washwashed 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

出典と根拠

ORDレコード
ord-56f9d98ea88740699b9b2bd887a4b231
出典データセット
uspto-grants-2000_08
特許番号
US06110919

反応ノート

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