4-Chlorophenol → tert-Butyl 6-[2-(4-chlorophenoxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 1370394Notes

Reaction equation

HRID 1370394 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.[Cl:25][C:26]1[CH:31]=[CH:30][C:29](O)=[CH:28][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([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)=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 46844-ChlorophenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22396751tert-butyl 6-(2-hydroxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 22396776tert-Butyl 6-[2-(4-chlorophenoxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 6-(2-hydroxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.533 g, 1.61 mmol), p-chlorophenol (0.224 g, 1.74 mmol, 1.08 equiv.) and triphenylphosphine (0.445 g, 1.70 mmol, 1.05 equiv.) was dissolved in THF (10 mL) and stirred at rt under N2. Diethyl azodicarboxylate (0.30 mL, 0.337 g, 1.93 mmol, 1.2 equiv.) was added, and the reaction mixture was stirred for 2.5 h. The reaction mixture was concentrated to give crude product (1.85 g), which was chromatographed (SiO2 175 g, eluted with 4:1 hexane:EtOAc) to give tert-butyl 6-[2-(4-chlorophenoxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.622 g) in 88% yield. 1H NMR (300 MHz, CD3OD) δ 1.48, 2.96-3.03, 3.05-3.14, 3.63-3.78, 4.15, 4.48, 6.70, 7.11, 7.15-7.20, 7.17, 7.27-7.31, 7.46-7.51; MS (ESI+) for C25H29ClN2O3 m/z 440.9 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred for 2.5 h
  2. concentrationThe reaction mixture was concentrated
  3. customto give crude product (1.85 g), which
  4. customwas chromatographed
  5. wash(SiO2 175 g, eluted with 4:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-f7e62de3baed4a45ad9606bdec23629d
Source dataset
uspto-grants-2003_06
Patent number
US06583135B2

Reaction notes

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