Hydrochloric Acid → (7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)-2-oxoquinolin-1(2h)-yl)methyl cyclohexyl carbonate hydrochloride

HRID 1774698Notes

Reaction equation

HRID 1774698 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]([CH:27]=[CH: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:45])([O:38][CH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1)[O:35][CH2:36][Cl:37].Cl>O1CCCC1>[ClH:37].[CH:39]1([O:38][C:34](=[O:45])[O:35][CH2:36][N:30]2[C:31]3[C:26](=[CH:25][CH:24]=[C:23]([O:22][CH2:21][CH2:20][CH2:19][CH2:18][N:15]4[CH2:14][CH2:13][N:12]([C:8]5[C:5]6[CH:6]=[CH:7][S:3][C:4]=6[CH:11]=[CH:10][CH:9]=5)[CH2:17][CH2:16]4)[CH:32]=3)[CH:27]=[CH:28][C:29]2=[O:33])[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 11978813BrexpiprazoleHCID 13603586Chloromethyl cyclohexyl carbonate

Product 1

HCID 117855958(7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)-2-oxoquinolin-1(2h)-yl)methyl cyclohexyl carbonate hydrochlorideYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydride (55% oil) (0.962 g, 22.04 mmol) was suspended in tetrahydrofuran (THF) (200 ml), 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)-butoxy]-1H-quinolin-2-one (8.31 g, 19.17 mmol) was added and the mixture was stirred at 50° C. for 1 hr. The mixture was cooled to 0° C., chloromethyl cyclohexyl carbonate (4.80 g, 24.92 mmol) was added dropwise and the mixture was stirred at room temperature overnight. After cooling to 0° C., excess 2N hydrochloric acid was added to quench the reaction. The precipitated solid was collected by filtration and dried. In addition, the filtrate was extracted with ethyl acetate. The organic layer was concentrated and purified by moderate-pressure silica gel column chromatography (methylene chloride:methanol=100:0 to 20:1). Likewise, the solid was purified by moderate-pressure silica gel column chromatography. Concentration under reduced pressure gave the title compound (yield, 5.04 g, 42%) as a white solid.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringthe mixture was stirred at room temperature overnight
  3. temperatureAfter cooling to 0° C.
  4. customto quench
  5. customthe reaction
  6. filtrationThe precipitated solid was collected by filtration
  7. customdried
  8. extractionIn addition, the filtrate was extracted with ethyl acetate
  9. concentrationThe organic layer was concentrated
  10. custompurified by moderate-pressure silica gel column chromatography (methylene chloride:methanol=100:0 to 20:1)
  11. customLikewise, the solid was purified by moderate-pressure silica gel column chromatography
  12. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-ec45c34668f340228b41cb252d8c7ee2
Source dataset
uspto-grants-2016_02
Patent number
US09260420B2

Reaction notes

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