Methanol → 3-(4-Methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octane

HRID 1295501ノート

反応式

HRID 1295501 の反応式
Cl[C:2]1([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=2)[CH:7]2[CH2:8][CH2:9][CH:3]1[CH2:4][N:5]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)[CH2:6]2.C(O)(C)(C)C.[Na].CO>O1CCOCC1>[CH3:18][O:17][C:14]1[CH:13]=[CH:12][C:11]([CH2:10][N:5]2[CH2:4][CH:3]3[CH:2]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=4)[CH:7]([CH2:8][CH2:9]3)[CH2:6]2)=[CH:16][CH:15]=1

参加物

6

反応物 4

HCID 887MethanolHCID 6386tert-ButanolHCID 5360545SodiumHCID 694314818-Chloro-3-(4-methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octane

生成物 1

HCID 694276763-(4-Methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octane収率 35%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

8-Chloro-3-(4-methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octane (2.46 g, 6.61 mmol) and t-butanol (9.48 mL, 99.1 mmol) in dioxane (25 mL) was heated to a gentle reflux with an oil bath (110° C.). Sodium (1.52 g, 66.1 mmol) was pre-washed sequentially with hexanes/ethanol/THF/hexanes then added portionwise to the above refluxing mixture over 20 min. The reaction mixture was heated overnight then cooled to room temperature. To this was added methanol (50 mL) to quench residual sodium. The solvent was removed in vacuo, and the product was partitioned between water (100 mL) and EtOAc (100 mL). The layers were separated and the product was further extracted with EtOAc (3×40 mL), washed with saturated aqueous NaCl solution (1×50 mL), dried over Na2SO4, filtered and concentrated to a light brown oil. Flash chromatography provided the title compound (780 mg, 35%). (TLC 20% EtOAc/hexanes Rf 0.60); 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J=8.7 Hz, 2H), 7.23 (t, J=7.7 Hz, 1H), 6.89 (d, J=8.7 Hz, 2H), 6.88 (m, 1H), 6.84 (s, 1H), 6.74 (dd, J=7.9, 2.5 Hz, 1H), 3.82 (s, 3H), 3.81 (s, 3H), 3.52 (s, 2H), 2.86 (dd, J=10.8, 3.7 Hz, 2H), 2.75 (s, 1H), 2.51 (br s, 2H), 2.28 (d, J=10.0 Hz, 2H), 1.79 (dd, J=12.7, 5.8 Hz, 2H), 1.63 (m, 2H); GCMS m/z 337 (M)+.

後処理

  1. additionthen added portionwise to the above refluxing mixture over 20 min
  2. temperatureThe reaction mixture was heated overnight
  3. temperaturethen cooled to room temperature
  4. customto quench residual sodium
  5. customThe solvent was removed in vacuo
  6. customthe product was partitioned between water (100 mL) and EtOAc (100 mL)
  7. customThe layers were separated
  8. extractionthe product was further extracted with EtOAc (3×40 mL)
  9. washwashed with saturated aqueous NaCl solution (1×50 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated to a light brown oil

出典と根拠

ORDレコード
ord-06bc1e66882440849e44c1be101b2bce
出典データセット
uspto-grants-2007_07
特許番号
US07241887B2

反応ノート

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