5,6,7,8-Tetrahydro-1-naphthol → HCID 22396857, compound

HRID 1370455Notes

Reaction equation

HRID 1370455 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[C:6]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17][C:5]1=2.[C:25]1(O)[C:34]2[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=2[CH:28]=[CH:27][CH:26]=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1>[C:33]1([O:1][CH2:2][CH2:3][N:4]2[C:12]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[C:6]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17][C:5]2=3)[C:34]2[CH2:25][CH2:26][CH2:27][CH2:28][C:29]=2[CH:30]=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 682585,6,7,8-Tetrahydro-1-naphtholHCID 97268Di-tert-butyl azodicarboxylateHCID 22396751tert-butyl 6-(2-hydroxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 22396857HCID 22396857, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

tert-Butyl 6-(2-hydroxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.100 g, 0.302 mmol) was dissolved in THF (6 mL). 5,6,7,8-Tetrahydronaphthalen-1-ol (0.067 g, 0.454 mmol) was added, and after 25 min di-tert-butyl azodicarboxylate (0.105 g, 0.454 mmol) was added. The reaction mixture was stirred at 40° C. for 5 h. The solvent was removed in vacuo. The crude product was flash chromatographed (9:1 hexane:EtOAc) and tert-butyl 6-[2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate was obtained in 22% yield. tert-Butyl 6-[2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.028 g, 0.061 mmol) was dissolved in EtOAc (5 mL). 4N HCl in dioxane (2 mL) was added. The reaction mixture was stirred at rt under N2 for 20 h. The solvent, was removed in vacuo. The crude product was dissolved in EtOAc (2 mL) and Et2O (3 mL) was added dropwise. The precipitate was collected by filtration, wash with Et2O and dried in vacuo at reduced pressure to yield 6-[2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)ethyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole hydrochloride in 73% yield. 1H NMR (400 MHz, CD3OD) δ 1.66-1.72, 2.35-2.39, 2.65-2.72, 3.20-3.23, 3.36-3.50, 4.23-4.28, 4.61-4.64, 6.51, 6.63, 6.93, 7.10, 7.18, 7.44, 7.50; MS (ESI+) for C24H28N2O m/z 361.1 (M+H)+.

Workup

  1. customThe solvent was removed in vacuo
  2. customchromatographed (9:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-5e5cb27a39ef480fab97c6ff30dd8bd2
Source dataset
uspto-grants-2003_06
Patent number
US06583135B2

Reaction notes

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