Sodium t-butoxide → HCID 25111756, compound

HRID 2242003Notes

Reaction equation

HRID 2242003 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:8]=[C:7]2[O:16][CH3:17].[CH3:19][C:20]([CH3:23])([O-:22])C.[Na+]>O1CCCC1.CCOCC.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:16]1[C:20]2([CH2:19][CH2:11][N:10]([C:2]3[CH:3]=[CH:4][C:5]([F:18])=[C:6]4[C:11]=3[N:10]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:8]=[C:7]4[O:16][CH3:17])[CH2:9][CH2:23]2)[O:22][CH2:6][CH2:7]1

Participants

6

Reactant 2

HCID 23676156Sodium t-butoxideHCID 251117558-Chloro-5-fluoro-4-methoxy-2-(trifluoromethyl)quinoline

Product 1

HCID 25111756HCID 25111756, compoundYield 126.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 8-chloro-5-fluoro-4-methoxy-2-(trifluoromethyl)quinoline (Step 2, 1.24 g, 4.45 mmol, 1 eq.) in anhydrous tetrahydrofuran (44 mL) was added tris(dibenzylideneacetone)-dipalladium(0) (Pd2(dba)3, 0.125 g, 0.14 mmol, 0.03 eq.), sodium tert-butoxide (0.69 g, 7.18 mmol, 1.61 eq.), 2-dicyclohexyl-phosphino-2′-(N,N-dimethylamino)biphenyl (CYMAP, 0.054 g, 0.14 mmol, 0.03 eq.), and 1,4-dioxo-8-azaspiro-4,5-decane (0.8 mL, 6.24 mmol, 1.4 eq.). The resulting mixture was stirred at 70° C. overnight (approximately 18 hours) under a nitrogen atmosphere. The reaction was then cooled to room temperature, diluted with ether, filtered through a plug of silica gel and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using hexane/ethyl acetate to give 1.09 g (64% yield) of the desired product as a beige solid; MP=101-103° C.; MS (ES) m/z (relative intensity): 387 (M+H)+ (100).

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. filtrationfiltered through a plug of silica gel
  3. concentrationconcentrated on a rotary evaporator
  4. customThe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-5e942ca827a14a1c91b93a1d3ba392ae
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

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