Triethylamine → methyl 1-(10,11-dihydro5H-dibenzo[a,d][7]annulen-5-yl)-1,2,5,6-tetrahydropyridine-3-carboxylate

HRID 736795

反応式

HRID 736795 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH2:10][NH:9][CH2:8][CH2:7][CH:6]=1)=[O:4].Cl.[CH2:12]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20](Cl)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13]1.N[C@H](C(O)=O)CC1C=C2C(C=CC=C2)=CC=1.C(N(CC)CC)C>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[CH2:10][N:9]([CH:20]2[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[CH2:13][CH2:12][C:26]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]2=3)[CH2:8][CH2:7][CH:6]=1)=[O:4]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 145875H-Dibenzo(a,d)cycloheptene, 10,11-dihydro-5-chloro-HCID 1859152-NaphthylalanineHCID 201540Norarecoline Hydrochloride

生成物 1

HCID 68816682methyl 1-(10,11-dihydro5H-dibenzo[a,d][7]annulen-5-yl)-1,2,5,6-tetrahydropyridine-3-carboxylate収率 67%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

To 7.338 g (41.31 mol) of guvacoline hydrochloride (Arzneim. Forsch. 1989, 39(5), 539. ) in dioxane (100 ml) was added 5-chloro-dibenzosuberane (14.933 g, 65.39 mmol), Nal (catalytic, ˜1 g), and triethylamine (17 mL, 122.0 mmol) to give a brown heterogeneous slurry that was heated at 90° C. overnight. The solvent was then concentrated and the resultant sludge was taken up in ethyl acetate and sequentially washed with Na2HPO4 buffer (pH 4), Na2CO3 (saturated aqueous), and brine. The organics were then dried over Na2SO4 and concentrated, resulting in a brown solid which was purified by chromatography on silica gel eluting with 1-5% ethyl acetate/hexanes to give 1-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester as a white solid (9.584 g, 28.74 mmol, 67%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 2.22 (dt, J=9.28, 2.68 Hz, 2H) 2.41 (t, J=5.56 Hz, 2H) 2.73-2.83 (m, 2H) 2.99-3.05 (m, 2H) 3.65 (s, 3 H) 3.90-4.00 (m, 2H) 4.11 (s, 1H) 6.94-6.99 (m, J=3.98, 3.98, 1.89, 1.77 Hz, 1 H) 7.05-7.11 (m, 4H) 7.13-7.21 (m, 4H).

後処理

  1. customto give a brown heterogeneous slurry that
  2. concentrationThe solvent was then concentrated
  3. washsequentially washed with Na2HPO4 buffer (pH 4), Na2CO3 (saturated aqueous), and brine
  4. dry with materialThe organics were then dried over Na2SO4
  5. concentrationconcentrated
  6. customresulting in a brown solid which
  7. customwas purified by chromatography on silica gel eluting with 1-5% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-6b34e9f6139d4ce4a80ed43d85bd86e7
出典データセット
uspto-grants-2009_09
特許番号
US07595327B2

関連ノート

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