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

HRID 2306957Notes

Reaction equation

HRID 2306957 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-39361219fd2f40c6ad4b759d23417ce0
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

Loading…