Ethanol → [4-(1-cyclopropylmethyl-6-ethoxy-3-iodo-1H-indol-2-yl)-phenyl]-carbamic acid isopropyl ester

HRID 502272Notes

Reaction equation

HRID 502272 reaction equation
[CH:1]1([CH2:4][N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH3:16])[CH:12]=3)[C:7]([I:17])=[C:6]2[C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][CH:19]=2)[CH2:3][CH2:2]1.[NH4+].[Cl-].C(O)C.[CH:32]([O:35][C:36](Cl)=[O:37])([CH3:34])[CH3:33]>O.C(Cl)Cl.[Fe].N1C=CC=CC=1>[CH:32]([O:35][C:36](=[O:37])[NH:24][C:21]1[CH:22]=[CH:23][C:18]([C:6]2[N:5]([CH2:4][CH:1]3[CH2:3][CH2:2]3)[C:13]3[C:8]([C:7]=2[I:17])=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH3:16])[CH:12]=3)=[CH:19][CH:20]=1)([CH3:34])[CH3:33]

Participants

9

Reactant 4

HCID 702EthanolHCID 7917Isopropyl chloroformateHCID 25517Ammonium ChlorideHCID 590304301-cyclopropylmethyl-6-ethoxy-3-iodo-2-(4-nitro-phenyl)-1H-indole

Product 1

HCID 59425548[4-(1-cyclopropylmethyl-6-ethoxy-3-iodo-1H-indol-2-yl)-phenyl]-carbamic acid isopropyl esterYield 58.1%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-Cyclopropylmethyl-6-ethoxy-3-iodo-2-(4-nitro-phenyl)-1H-indole (990 mg, 2.14 mmol), iron powder (690 mg, 11.8 mmol), NH4Cl (690 mg, 12.9 mmol), ethanol (22 mL), and H2O (8 mL) were heated at 80° C. for 90 minutes. The reaction mixture was diluted with H2O and extracted with CH2Cl2. The organic layer was dried, concentrated and purified by silica gel chromatography (CH2Cl2). Product containing fractions were used immediately in the next reaction. The compound in CH2Cl2 (80 mL) was treated with pyridine (15 mL) and isopropylchloroformate (1M in toluene, 2.5 mL, 2.5 mmol) and stirred at room temperature for 15 minutes. The reaction mixture was concentrated and extracted with a mixture of EtOAc and aq. HCl. The organic layer was washed with H2O and brine and then dried, concentrated and purified by silica gel chromatography (CH2Cl2/hexane, 1:1 to 3:1) to provide [4-(1-cyclopropylmethyl-6-ethoxy-3-iodo-1H-indol-2-yl)-phenyl]-carbamic acid isopropyl ester (644 mg, 58%) as a white solid.

Workup

  1. extractionextracted with CH2Cl2
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. custompurified by silica gel chromatography (CH2Cl2)
  5. additionProduct containing fractions
  6. customwere used immediately in the next reaction
  7. concentrationThe reaction mixture was concentrated
  8. extractionextracted with a mixture of EtOAc and aq. HCl
  9. washThe organic layer was washed with H2O and brine
  10. customdried
  11. concentrationconcentrated
  12. custompurified by silica gel chromatography (CH2Cl2/hexane, 1:1 to 3:1)

Sources & evidence

ORD record
ord-3dc53c2837484bc5a7a22155addca3ae
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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