Hydrochloric Acid → (5R,6S)-rel-13-Cyclohexyl-6,7-dihydro-5,6-dihydroxy-5H-indolo[2,1-a}[2]benzazepine-10-carboxylic acid

HRID 860740Notes

Reaction equation

HRID 860740 reaction equation
[OH-].[Na+].[CH:3]1([C:9]2[C:10]3[CH:11]=[CH:12][C:13]([C:29]([O:31]C)=[O:30])=[CH:14][C:15]=3[N:16]3[CH2:22][C@H:21]([OH:23])[C@H:20]([OH:24])[C:19]4[CH:25]=[CH:26][CH:27]=[CH:28][C:18]=4[C:17]=23)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Cl>CO.O1CCCC1>[CH:3]1([C:9]2[C:10]3[CH:11]=[CH:12][C:13]([C:29]([OH:31])=[O:30])=[CH:14][C:15]=3[N:16]3[CH2:22][C@H:21]([OH:23])[C@H:20]([OH:24])[C:19]4[CH:25]=[CH:26][CH:27]=[CH:28][C:18]=4[C:17]=23)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69207219Methyl (5r,6s)-rel-13-cyclohexyl-6,7-dihydro-5,6-dihydroxy-5h-indolo[2,1-a][2]benzazepine-10-carboxylate

Product 1

HCID 69207235(5R,6S)-rel-13-Cyclohexyl-6,7-dihydro-5,6-dihydroxy-5H-indolo[2,1-a}[2]benzazepine-10-carboxylic acidYield 94%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

Sodium hydroxide (0.2′ 1 mL of 1 N, 0.2 mmol) was added to a solution of methyl (5R,6S)-rel-13-cyclohexyl-6,7-dihydro-5,6-dihydroxy-5H-indolo[2,1-a][2]benzazepine-10-carboxylate (20 mg, 0.049 mmol) in methanol (0.5 mL) and tetrahydrofuran (0.5 mL) in a microwave vial. The vial was sealed and the contents heated at 90° C. for 7 min in a microwave apparatus. The solution was acidified with dilute hydrochloric acid and a precipitate was observed to form. The solid was collected by filtration and purified on the Prep. reverse phase HPLC. The product containing fraction was concentrated on a Speed Vac® to leave the titled compound as a white solid (18 mg, 94%). ESI-MS m/z 392 (MH+) 1H NMR (500 MHz, MeOD) δ 1.25–1.34 (m, 1 H) 1.39–1.54 (m, 2 H) 1.60–1.67 (m, 1 H) 1.77–1.86 (m, 2 H) 1.93–2.00 (m, 1 H) 2.01–2.17 (m, 3 H) 2.93–3.02 (m, 1 H) 3.36 (m, 1 H) 4.43 (d, J=4.27 Hz, 1 H) 4.54 (m, 1 H) 4.72 (dd, J=14.19, 7.17 Hz, 1 H) 7.46 (m, 2 H) 7.53 (m, 1 H) 7.74 (dd, J=8.39, 1.37 Hz, 1 H) 7.79 (d, J=7.63 Hz, 1 H) 7.90 (d, J=8.24 Hz, 1 H) 8.19 (s, 1 H).

Workup

  1. customThe vial was sealed
  2. customto form
  3. filtrationThe solid was collected by filtration
  4. custompurified on the Prep
  5. additionThe product containing fraction
  6. concentrationwas concentrated on a Speed Vac®

Sources & evidence

ORD record
ord-1e8316b8e15748c4abad3094e7df4516
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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