Triethylamine → 2-Methyl-3-methylthio-4-morpholino-5-fluoro-7-bromoindole

HRID 1583606Notes

Reaction equation

HRID 1583606 reaction equation
[Br:1][C:2]1[CH:8]=[C:7]([F:9])[C:6]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:5][C:3]=1[NH2:4].ClOC(C)(C)C.[CH3:22][S:23][CH2:24][C:25](=O)[CH3:26].C(N(CC)CC)C>C(Cl)Cl.O>[CH3:26][C:25]1[NH:4][C:3]2[C:5]([C:24]=1[S:23][CH3:22])=[C:6]([N:10]1[CH2:11][CH2:12][O:13][CH2:14][CH2:15]1)[C:7]([F:9])=[CH:8][C:2]=2[Br:1]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 521297Tert-Butyl hypochloriteHCID 64307131-Methylthio-2-propanoneHCID 202589772-Bromo-4-fluoro-5-morpholinoaniline

Product 1

HCID 202589822-Methyl-3-methylthio-4-morpholino-5-fluoro-7-bromoindoleYield 79.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 145 g of 2-bromo-4-fluoro-5-morpholinoaniline in 1 l of methylene chloride and the solution was cooled to a temperature of not higher than -50° C. on a dry ice-acetone bath. At the same temperature as above 60 g of tert-butyl hypochlorite was added dropwise to the solution during which operation the reaction system changed from heterogeneous mixture to homogeneous solution. Then, 67 g of methylthio-2-propanone was added dropwise to the solution and the mixture was reacted at the same temperature as above for 2 hours followed by adding dropwise 80 ml of triethylamine. After completion of addition, the temperature of the mixture was elevated slowly to room temperature. After room temperature was attained 1 l of water was added to separate the methylene chloride layer which then was dried over sodium sulfate and concentrated under reduced pressure to give 150 g of 2-methyl-3-methylthio-5-fluoro-4-morpholino-7-bromoindole.

Workup

  1. customthe mixture was reacted at the same temperature as above for 2 hours
  2. additionAfter completion of addition
  3. customwas elevated slowly to room temperature
  4. customAfter room temperature
  5. additionwas added
  6. customto separate the methylene chloride layer which
  7. dry with materialthen was dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e1d2f40abd2e427ea0a895c75dca11d9
Source dataset
uspto-grants-1985_11
Patent number
US04552879

Reaction notes

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