Thiophenol → tert-butyl 6-[2-(phenylsulfanyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 1370395Notes

Reaction equation

HRID 1370395 reaction equation
O[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.CS(Cl)(=O)=O.[C:30]1([SH:36])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[OH-].[K+]>C(Cl)Cl.CN(C=O)C.C(N(CC)CC)C>[C:30]1([S:36][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)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 4

HCID 7969ThiophenolHCID 14797Potassium HydroxideHCID 31297Methanesulfonyl chloride2×HCID 22396751tert-butyl 6-(2-hydroxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 22396645tert-butyl 6-[2-(phenylsulfanyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylateYield 28%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

tert-Butyl 6-(2-hydroxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate, (0.0488 g, 0.148 mmol) was dissolved in CH2Cl2 (5 mL) and stirred at rt. Triethylamine (5 mL) was added, followed by methanesulfonyl chloride (0.017 mL, 0.221 mmol, 1.50 equiv.). The reaction mixture was stirred for 2 h, and additional methanesulfonyl chloride (0.015 mL) was added. After 30 min, a mixture of thiophenol (0.065 mL, 0.592 mmol, 4.0 equiv.) and KOH (12 equiv.) in DMF (5 mL) was added, and the resulting mixture was stirred for 30 min. The reaction mixture was quenched with saturated aqueous NH4Cl, then the resulting mixture was extracted with CH2Cl2 (3×). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude product was purified by PTLC (1 mm×20 cm×20 cm SiO2 plates, developed with 1:4 EtOAc:hexane) to give tert-butyl 6-[2-(phenylsulfanyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.017 g) in 28% yield as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.52, 2.92, 2.99, 3.17, 3.66-3.73, 4.28, 7.10-7.20, 7.25-7.41, 7.48; MS (ESI+) for C25H30N2O2S m/z 423 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred for 2 h
  2. additionwas added
  3. stirringthe resulting mixture was stirred for 30 min
  4. customThe reaction mixture was quenched with saturated aqueous NH4Cl
  5. extractionthe resulting mixture was extracted with CH2Cl2 (3×)
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by PTLC (1 mm×20 cm×20 cm SiO2 plates, developed with 1:4 EtOAc:hexane)

Sources & evidence

ORD record
ord-4f053ea415f34b6fbf3920b275912ce3
Source dataset
uspto-grants-2003_06
Patent number
US06583135B2

Reaction notes

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