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

HRID 736795

Reaction equation

HRID 736795 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-6b34e9f6139d4ce4a80ed43d85bd86e7
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Linked notes

Loading…