Water → methyl 13-cyclohexyl-6,7-dihydro-6-oxo-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

HRID 860742Notes

Reaction equation

HRID 860742 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH:12]1([C:18]2[C:19]3[CH:20]=[CH:21][C:22]([C:38]([O:40][CH3:41])=[O:39])=[CH:23][C:24]=3[N:25]3[CH2:31][C@H:30]([OH:32])[C@H:29](O)[C:28]4[CH:34]=[CH:35][CH:36]=[CH:37][C:27]=4[C:26]=23)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.O>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH:12]1([C:18]2[C:19]3[CH:20]=[CH:21][C:22]([C:38]([O:40][CH3:41])=[O:39])=[CH:23][C:24]=3[N:25]3[CH2:31][C:30](=[O:32])[CH2:29][C:28]4[CH:34]=[CH:35][CH:36]=[CH:37][C:27]=4[C:26]=23)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1

Participants

6

Reactant 3

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 69207219Methyl (5r,6s)-rel-13-cyclohexyl-6,7-dihydro-5,6-dihydroxy-5h-indolo[2,1-a][2]benzazepine-10-carboxylate

Product 1

HCID 58765241methyl 13-cyclohexyl-6,7-dihydro-6-oxo-5H-indolo[2,1-a][2]benzazepine-10-carboxylateYield 62%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

p-Toluenesulfonic acid (50 mg, 0.29 mmol) was added to methyl 13-cyclohexyl-6,7-dihydro-(5R,6S)-rel-5,6-dihydroxy-5H-indolo[2,1-a][2]benzazepine-10-carboxylate (100 mg, 0.25 mmol) in 50 mL of dry toluene. The solution was heated under reflux for 18 hr with removal of water using a Dean-Stark trap. The solution was diluted with ethyl acetate and washed with brine (3×) and dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified utilizing a Biotage apparatus with a prepacked silica column and using gradients of hexanes:ethyl acetate of from (98:2) to (85:15) to afford the product as a light yellow solid (60 mg, 62%). ESI-MS m/z 388 (MH+); 1H NMR (500 MHz, CHLOROFORM-D) □ 1.22–1.68 (m, 4 H) 1.73–1.83 (m, 2 H) 1.91–1.99 (m, 1 H) 2.02–2.15 (m, 3 H) 2.95 (m, 1 H) 3.57 (d, J=14.04 Hz, 1 H) 3.84 (d, J=14.04 Hz, 1 H) 3.95 (s, 3 H) 4.44 (d, J=18.01 Hz, 1 H) 4.96 (d, J=18.01 Hz, 1 H) 7.35 (d, J=7.63 Hz, 1 H) 7.43 (m, 1 H) 7.48 (t, J=7.32 Hz, 1 H) 7.54 (m, 1 H) 7.81 (d, J=8.55 Hz, 1 H) 7.92 (d, J=8.55 Hz, 1 H) 8.09 (s, 1 H).

Workup

  1. temperatureThe solution was heated
  2. washwashed with brine (3×)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-e9b9465c15164a13996d9ae650636581
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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