Hydrochloric Acid → HCID 25147039, compound

HRID 1392992Notes

Reaction equation

HRID 1392992 reaction equation
[H-].[K+].Br[C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2.[Br:13][C:14]1[CH:25]=[CH:24][C:17]([C:18](N(OC)C)=[O:19])=[CH:16][CH:15]=1.Cl>C(OCC)C.CCCCCC>[Br:13][C:14]1[CH:25]=[CH:24][C:17]([C:18]([C:12]2[CH:11]=[C:10]3[C:6]([CH:7]=[CH:8][NH:9]3)=[CH:5][CH:4]=2)=[O:19])=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 249055-BromoindoleHCID 82127Potassium hydrideHCID 109992524-Bromo-N-methoxy-N-methylbenzamide

Product 1

HCID 25147039HCID 25147039, compoundYield 48.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To hexane washed potassium hydride (0.30 g, 1.5 mmol), suspended in anhydrous diethylether (1.5 mL), was added 5-bromoindole (0.241 g, 1.23 mmol) dissolved in diethyl ether (2.0 mL) at 0° C. After 15 min, the mixture was cooled to −78 ° C. and tert-buthyllithium (1.5 mL, 2.55 mmol), pre-cooled to −78° C., was added via cannula. After 10 min 4-bromo-N-methoxy-N-methylbenzamide (0.30 g, 1.2 mmol) in diethylether (2.0 mL), pre-cooled to −78° C., was added. The reaction mixture was kept at −78° C. for 10 min and then allowed to warm up to room temperature and stirred for another hour. HCl (1M, 5 mL) was added and the mixture stirred for 15 min. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with water and brine, dried over MgSO4, and the solvent was evaporated. The crude product was purified by flash column chromatography on silica using methylene chloride as the eluent affording 176 mg (48% yield) of the title compound as a pale yellow solid: mp 47-49° C.; 1H NMR (400 MHz, CDCl3) δ 8.55 (br s, 1 H), 8.01 (s, 1 H), 7.87 (m, 2 H), 7.72 (m, 2 H), 7.68 (dd, J=8.2 Hz, J=1.4 Hz, 1 H), 7.52 (m, 1 H), 7.35 (s, 1 H), 6.74 (m, 1 H); 13C NMR (100.5 MHz, CDCl3) δ 196.5, 138.0, 135.4, 132.0, 131.9, 131.8, 131.4, 128.5, 127.1, 122.4, 120.8, 114.6, 103.6; MS TSP) m/z 300, 302 (M+1).

Workup

  1. temperaturetert-buthyllithium (1.5 mL, 2.55 mmol), pre-cooled to −78° C.
  2. additionwas added via cannula
  3. temperaturepre-cooled to −78° C.
  4. additionwas added
  5. waitThe reaction mixture was kept at −78° C. for 10 min
  6. temperatureto warm up to room temperature
  7. stirringthe mixture stirred for 15 min
  8. customThe phases were separated
  9. extractionthe aqueous phase was extracted with ethyl acetate
  10. washThe combined organic phases were washed with water and brine
  11. dry with materialdried over MgSO4
  12. customthe solvent was evaporated
  13. customThe crude product was purified by flash column chromatography on silica

Sources & evidence

ORD record
ord-ce2355acbd6c4d1e8cfbc46b6fabc62d
Source dataset
uspto-grants-2008_03
Patent number
US07345050B2

Reaction notes

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