Hydrochloric Acid → ethyl 1-((9RS,10RS)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-piperidine carboxylate

HRID 862729ノート

反応式

HRID 862729 の反応式
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17](O)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.S(Cl)(Cl)=O.[NH:24]1[CH2:34][CH2:33][CH:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:26][CH2:25]1.Cl>C1(C)C=CC=CC=1.CN(C)C=O>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17]([N:24]4[CH2:25][CH2:26][CH:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:33][CH2:34]4)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 70770Ethyl 4-piperidinecarboxylateHCID 196986472-Chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid

生成物 1

HCID 19698629ethyl 1-((9RS,10RS)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-piperidine carboxylate収率 87%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 1140Toluene溶媒

実験手順

A suspension of (9RS,10RS)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid (7.50 g, 27.7 mmol), prepared as described in Example 1j, in toluene (75 mL) was treated with thionyl chloride (4.12 g, 34.6 mmol) and N,N-dimethylformamide (2 drops). The mixture was heated to reflux for 3 h, then was cooled to room temperature and treated with ethyl isonipecotate (10.88 g, 69.25 mmol). The resulting thick slurry was stirred at room temperature for 16 h, then was poured into 1N hydrochloric acid (100 mL) and extracted with ethyl acetate (3×100 mL). The organic extracts were washed sequentially with 1N hydrochloric acid (100 mL), 10% aqueous sodium bicarbonate (100 mL) and brine (100 ml), combined, dried (MgSO4), filtered and evaporated to leave an amber oil which solidified on standing. The crystalline product was triturated with hexane (300 mL) and ether (25 mL), isolated by filtration, washed with hexane/ether (10:1, 50 mL) and air dried to afford the title compound (9.83 g, 23.9 mmol, 87%) as a white solid. 1H NMR (d6-DMSO): δ7.5 (br, 1H, H--C(1)), 7.35 (m, 3H), 7.01 (m, 3H), 4.5 (br, 1H), 4.43 (s, 1H, H--C(10)), 4.08 (q, J=7.0 Hz, 2H, CH2CH3), 3.6 (br, 1H), 3.2-2.55 (brm, 6H), 2.05-1.45 (brm, 5H), 1.19 (t, J=7.0 Hz, 3H, CH2CH3).

後処理

  1. customprepared
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 3 h
  4. extractionextracted with ethyl acetate (3×100 mL)
  5. washThe organic extracts were washed sequentially with 1N hydrochloric acid (100 mL), 10% aqueous sodium bicarbonate (100 mL) and brine (100 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto leave an amber oil which
  10. customThe crystalline product was triturated with hexane (300 mL) and ether (25 mL)
  11. customisolated by filtration
  12. washwashed with hexane/ether (10:1, 50 mL) and air
  13. customdried

出典と根拠

ORDレコード
ord-d366381fc61942129159e8d3335a542d
出典データセット
uspto-grants-1998_02
特許番号
US05719166

反応ノート

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