Sodium hydride → benzoic acid 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-1-yl)butoxy]-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester

HRID 1774677Notes

Reaction equation

HRID 1774677 reaction equation
[H-].[Na+].[S:3]1[CH:7]=[CH:6][C:5]2[C:8]([N:12]3[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][CH2:21][O:22][C:23]4[CH:32]=[C:31]5[C:26]([CH2:27][CH2:28][C:29](=[O:33])[NH:30]5)=[CH:25][CH:24]=4)[CH2:14][CH2:13]3)=[CH:9][CH:10]=[CH:11][C:4]1=2.[C:34]([O:42][CH2:43]Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[Cl-].[NH4+]>O1CCCC1>[S:3]1[CH:7]=[CH:6][C:5]2[C:8]([N:12]3[CH2:13][CH2:14][N:15]([CH2:18][CH2:19][CH2:20][CH2:21][O:22][C:23]4[CH:32]=[C:31]5[C:26]([CH2:27][CH2:28][C:29](=[O:33])[N:30]5[CH2:43][O:42][C:34](=[O:41])[C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)=[CH:25][CH:24]=4)[CH2:16][CH2:17]3)=[CH:9][CH:10]=[CH:11][C:4]1=2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 79257Chloromethyl benzoateHCID 118572457-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-3,4-dihydro-1H-quinolin-2-one

Product 1

HCID 89435469benzoic acid 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-1-yl)butoxy]-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl esterYield 86.55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (55% oil) (0.15 g, 2.52 mmol) was suspended in tetrahydrofuran (THF) (20 ml) and, under a nitrogen atmosphere, 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-1-yl)butoxy]-3,4-dihydro-1H-quinolin-2-one (1.0 g, 2.30 mmol) synthesized in the same manner as in WO2006/112464 (Example 11) was added, and the mixture was stirred with heating under reflux for 25 min. The mixture was cooled to 0° C., chloromethyl benzoate (0.627 g, 3.67 mmol) was added, and the mixture was stirred at room temperature for 2.5 hr. Under ice-cooling, aqueous ammonium chloride was added to the reaction mixture to discontinue the reaction, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by moderate-pressure silica gel column chromatography (hexane:ethyl acetate=1:0 to 2:3) and concentrated under reduced pressure to give the title compound (yield 1.132 g, 86.55%) as a colorless amorphous solid.

Workup

  1. additionwas added
  2. temperaturewith heating
  3. temperatureunder reflux for 25 min
  4. stirringthe mixture was stirred at room temperature for 2.5 hr
  5. temperatureUnder ice-cooling
  6. customthe reaction
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by moderate-pressure silica gel column chromatography (hexane:ethyl acetate=1:0 to 2:3)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-42fb205c20864248b19c4e7495736983
Source dataset
uspto-grants-2016_02
Patent number
US09260420B2

Reaction notes

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