Hydrochloric Acid → HCID 22396676, compound

HRID 2307021Notes

Reaction equation

HRID 2307021 reaction equation
[C:1]1([O:11][CH2:12][CH2:13][N:14]2[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:16]3[CH2:23][CH2:24][N:25](C(OC(C)(C)C)=O)[CH2:26][CH2:27][C:15]2=3)[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[ClH:35]>CCOC(C)=O.O1CCOCC1>[ClH:35].[C:1]1([O:11][CH2:12][CH2:13][N:14]2[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:16]3[CH2:23][CH2:24][NH:25][CH2:26][CH2:27][C:15]2=3)[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 22396857HCID 22396857, compound

Product 1

HCID 22396676HCID 22396676, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

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. dissolutionThe crude product was dissolved in EtOAc (2 mL)
  3. additionEt2O (3 mL) was added dropwise
  4. filtrationThe precipitate was collected by filtration
  5. washwash with Et2O
  6. customdried in vacuo at reduced pressure

Sources & evidence

ORD record
ord-65622dcf304b4ed78e1834acf3702471
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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