Chlorosulfonyl isocyanate → 4-[1-carbamoyl-5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester

HRID 1739586Notes

Reaction equation

HRID 1739586 reaction equation
[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[NH:13][CH:12]=2)=[C:6]([O:23][CH3:24])[CH:5]=1.ClS([N:30]=[C:31]=[O:32])(=O)=O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]([C:31](=[O:32])[NH2:30])[CH:12]=2)=[C:6]([O:23][CH3:24])[CH:5]=1

Participants

4

Reactant 2

HCID 70918Chlorosulfonyl isocyanateHCID 114732633-(2-Methoxy-4-methoxycarboxybenzyl)-5-nitroindole

Product 1

HCID 543251484-[1-carbamoyl-5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylesterYield 30.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester (5.04 grams, 14.80 mmol) in methylene chloride (150 mL) was added chlorosulfonylisocyanate (1.3 mL, 14.80 mmol) and the resulting solution was stirred for 5 days at room temperature. The solution was then concentrated in vacuo, and the crude product dissolved in a 6:1 ratio of acetone:water (180 mL). The pH of this solution was adjusted to approx. 8 by the addition of 2 M sodium hydroxide (aq). The resulting mixture was stirred, at room temperature, for 45 minutes. The reaction was diluted with water (300 mL) and the resulting suspension was stirred for 30 minutes. Filtration, followed by trituration of the solid in methanol gave 4-[1-carbamoyl-5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester (1.75 grams). The filtrate was concentrated, and the crude chromatographed on silica gel (2.5% methanol/methylene chloride) to give additional 4-[1-carbamoyl-5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester (0.36 grams, 37% yield overall).

Workup

  1. concentrationThe solution was then concentrated in vacuo
  2. dissolutionthe crude product dissolved in a 6:1 ratio of acetone
  3. additionby the addition of 2 M sodium hydroxide (aq)
  4. stirringThe resulting mixture was stirred, at room temperature, for 45 minutes
  5. additionThe reaction was diluted with water (300 mL)
  6. stirringthe resulting suspension was stirred for 30 minutes
  7. filtrationFiltration

Sources & evidence

ORD record
ord-c5673d4f5fed4c6ba93d0318e5f61665
Source dataset
uspto-grants-1999_10
Patent number
US05965745

Reaction notes

Loading…