Triethylamine → 7-(4-fluorophenethyl)-10-chloro-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole

HRID 2167811Notes

Reaction equation

HRID 2167811 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]4[CH:17]([C:5]=3[C:4]=2[CH:3]=1)[CH2:16][CH2:15][CH2:14]4.Br[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1.C(N(CC)CC)C.CCOC(C)=O>CCO>[F:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][CH2:19][N:7]2[C:8]3[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=3[C:5]3[CH:17]4[N:13]([CH2:12][CH2:11][C:6]2=3)[CH2:14][CH2:15][CH2:16]4)=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 5731534-Fluorophenethyl bromideHCID 6743193010-chloro-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole

Product 1

HCID 513560977-(4-fluorophenethyl)-10-chloro-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 7-chloro-2,3,5,10,11,11c-hexahydro-1H-indolizino[7,6-b]indole and 10-chloro-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (non-separable regioisomers, 500 mg, 2.03 mmol, 1 equiv) and 1-(2-bromoethyl)-4-fluorobenzene (577 mg, 2.84 mmol, 1.4 equiv) were heated at 95° C. with triethyl amine (0.85 mL, 6.09 mmol, 3 equiv) in 6 mL of EtOH for 18 h. The mixture was brought to RT followed by dilution with EtOAc (40 mL), washed with water (2×10 mL), and once with brine, then dried over sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography over 230-400-mesh silica gel using a gradient of MeOH in EtOAc (0 to 50%). The product was further purified by reverse phase HPLC. Column: ZORBAX SB C18, 4.6×250 mm, 5μ, retention time (min): 9.71, purity: 95.20%;

Workup

  1. customwas brought to RT
  2. washwashed with water (2×10 mL)
  3. dry with materialonce with brine, then dried over sodium sulfate
  4. customevaporated under reduced pressure
  5. customThe crude product was purified by column chromatography over 230-400-mesh silica gel using a gradient of MeOH in EtOAc (0 to 50%)
  6. customThe product was further purified by reverse phase HPLC

Sources & evidence

ORD record
ord-7fe580b4c2264233ac80bf59f16b6b73
Source dataset
uspto-grants-2015_06
Patent number
US09045482B2

Reaction notes

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