tert-Butyl methyl ether → {2-[6-Chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 1097835Notes

Reaction equation

HRID 1097835 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].[C:23]([O:27][C:28]([N:30]1[CH2:34][CH2:33]OS1(=O)=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].COC(C)(C)C>CN(C)C=O>[C:23]([O:27][C:28](=[O:29])[NH:30][CH2:34][CH2:33][N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=2)[C:6]([C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])=[CH:7]1)([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 15413tert-Butyl methyl etherHCID 224972521-(6-Chloro-3-indolyl)-2,2,2-trifluoroethanone2×HCID 235840203-Boc-1,2,3-oxathiazolidine 2,2-dioxideHCID 23665647Potassium tert-butoxide

Product 1

HCID 66810786{2-[6-Chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-ethyl}-carbamic acid tert-butyl esterYield 61.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 11.5 g (46.4 mmol) 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone in 150 ml N,N-dimethylformamide were slowly added 6.25 g (55.7 mmol) potassium tert-butylate. The temperature was kept below 32° C. The reaction mixture was allowed to cool to room temperature and stirred for 20 min. To the resulting brown suspension were added slowly 12.4 g (55.7 mmol) 2,2-dioxo-2λ6-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester. The reaction mixture was stirred at room temperature until complete consumption of 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone, which was monitored by thin layer chromatography. Dilution with 300 ml tert-butyl methyl ether was followed by washing with 250 ml of a 0.2 M aqueous solution of hydrochloric acid. The aqueous layer was extracted with two 200-ml portions of tert-butyl methyl ether. The combined organic layers were washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The residue, 19.5 g of a light brown solid, was triturated with 300 ml of warm tert-butyl methyl ether. After cooling to room temperature the precipitate was collected by filtration, washed with cold tert-butyl methyl ether and dried in vacuo to give 11.1 g (61%) of the title compound as an off-white solid. The filtrate was concentrated to dryness. The residue was triturated with 50 ml warm tert-butyl methyl ether. After cooling to room temperature the precipitate was collected by filtration, washed with cold tert-butyl methyl ether and dried in vacuo to give another 3.5 g (19%) of the title compound as an off-white solid.

Workup

  1. customwas kept below 32° C
  2. washby washing with 250 ml of a 0.2 M aqueous solution of hydrochloric acid
  3. extractionThe aqueous layer was extracted with two 200-ml portions of tert-butyl methyl ether
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue, 19.5 g of a light brown solid, was triturated with 300 ml of warm tert-butyl methyl ether
  8. temperatureAfter cooling to room temperature the precipitate
  9. filtrationwas collected by filtration
  10. washwashed with cold tert-butyl methyl ether
  11. customdried in vacuo

Sources & evidence

ORD record
ord-4b4263e3800f4ef298bdff0031cbc781
Source dataset
uspto-grants-2012_03
Patent number
US08143281B2

Reaction notes

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