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Hexamethyldisilazane → 2-[4-(1-Methylpiperidin-4-ylidene)-4,10-dihydro-9-oxa-3-thiabenzo[f]azulen-6-yl]propionic acid hydrochloride

HRID 389022
Notes
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Reaction equation

HRID 389022 reaction equation
C[Si](C)(C)N[Si](C)(C)C.C([Li])CCC.CCCCCC.[C:21]([O:25]C(C)(C)C)(=[O:24])[CH2:22][CH3:23].CC(C1C=CC=C(C(C)C)C=1N1C=[N+](C2C(C(C)C)=CC=CC=2C(C)C)CC1)C.[Cl-:59].Br[C:61]1[CH:62]=[CH:63][C:64]2[O:73][CH2:72][C:71]3[CH:70]=[CH:69][S:68][C:67]=3[C:66](=[C:74]3[CH2:79][CH2:78][N:77]([CH3:80])[CH2:76][CH2:75]3)[C:65]=2[CH:81]=1.Cl.O1CCOCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O.C1(C)C=CC=CC=1>[ClH:59].[CH3:80][N:77]1[CH2:78][CH2:79][C:74](=[C:66]2[C:65]3[CH:81]=[C:61]([CH:22]([CH3:23])[C:21]([OH:25])=[O:24])[CH:62]=[CH:63][C:64]=3[O:73][CH2:72][C:71]3[CH:70]=[CH:69][S:68][C:67]2=3)[CH2:75][CH2:76]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 6

HCID 13838HexamethyldisilazaneHCID 88561tert-Butyl propionateHCID 27349181,3-Bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazol-3-ium chlorideHCID 204431481,4-Dioxane hydrochlorideHCID 684907724-(6-Bromo-10H-9-oxa-3-thiabenzo[f]azulen-4-ylidene)-1-methylpiperidineHCID 178418244HCID 178418244, compound

Product 1

HCID 684884562-[4-(1-Methylpiperidin-4-ylidene)-4,10-dihydro-9-oxa-3-thiabenzo[f]azulen-6-yl]propionic acid hydrochlorideYield 461.9%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Hexamethyldisilazane (5.0 mL, 31.2 mmol) was ice-cooled in an argon atmosphere, and a 1.6 mol/L butyllithium-hexane solution (19.5 mL, 31.2 mmol) was added dropwise thereto. After stirring the mixture for 30 minutes, t-butyl propionate (2.1 g, 16.1 mmol) was added dropwise to the solution, and stirred for 30 minutes. Further, Pd(dba)2 (0.45 g, 0.8 mmol) and N,N′-(2,6-diisopropylphenyl)dihydroimidazolium chloride (0.34 g, 0.8 mmol) were added thereto, the mixture was stirred for 10 minutes, and a toluene (25 mL) solution of 4-(6-bromo-10H-9-oxa-3-thiabenzo[f]azulen-4-ylidene)-1-methylpiperidine (3.0 g, 8.0 mmol) was then added dropwise thereto. The mixture was stirred overnight at room temperature, water was then added to the reaction mixture, and the product was extracted with ethyl acetate. The solvents in the organic layer were distilled off under a reduced pressure, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate). The purified compound was dissolved in dioxane (10 mL), a 4 mol/L hydrogen chloride-dioxane solution (12.5 mL, 50 mmol) was added to the solution, and the mixture was stirred overnight. The solvents were distilled off under a reduced pressure, and the precipitated crystals were collected by filtration, to give 1.5 g (69%) of the captioned compound.

Workup

  1. temperaturecooled in an argon atmosphere
  2. stirringstirred for 30 minutes
  3. stirringthe mixture was stirred for 10 minutes
  4. stirringThe mixture was stirred overnight at room temperature
  5. extractionthe product was extracted with ethyl acetate
  6. distillationThe solvents in the organic layer were distilled off under a reduced pressure
  7. customthe residue was purified by silica gel column chromatography (hexane-ethyl acetate)
  8. dissolutionThe purified compound was dissolved in dioxane (10 mL)
  9. stirringthe mixture was stirred overnight
  10. distillationThe solvents were distilled off under a reduced pressure
  11. filtrationthe precipitated crystals were collected by filtration

Sources & evidence

ORD record
ord-8f6c830543e3480a82bca019922a2442
Source dataset
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08377967B2

Reaction notes

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