Binap, (A+-)- → 1-[5-(Morpholin-4-ylcarbonyl)-4-(trifluoromethyl)pyrimidin-2-yl]-6-nitro-1,2,3,4-tetrahydroquinoline

HRID 38782Notes

Reaction equation

HRID 38782 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][N:3]=1.[N+:20]([C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH2:28][CH2:27][CH2:26]2)([O-:22])=[O:21].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>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.C1(C)C=CC=CC=1>[N:14]1([C:12]([C:5]2[C:6]([C:8]([F:11])([F:10])[F:9])=[N:7][C:2]([N:29]3[C:30]4[C:25](=[CH:24][C:23]([N+:20]([O-:22])=[O:21])=[CH:32][CH:31]=4)[CH2:26][CH2:27][CH2:28]3)=[N:3][CH:4]=2)=[O:13])[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 70641106-Nitro-1,2,3,4-tetrahydroquinolineHCID 23676156Sodium t-butoxideHCID 581687074-{[2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}morpholine

Product 1

HCID 581687841-[5-(Morpholin-4-ylcarbonyl)-4-(trifluoromethyl)pyrimidin-2-yl]-6-nitro-1,2,3,4-tetrahydroquinolineYield 27.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-{[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}morpholine (150 mg), 6-nitro-1,2,3,4-tetrahydroquinoline (136 mg), tris(dibenzylideneacetone)dipalladium(0) (14 mg), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (19 mg), sodium tert-butoxide (98 mg), and toluene (2 mL) was stirred at 110° C. for 30 minutes under radiation with microwave. To the reaction mixture was added water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate), and the obtained residue was solidified from a mixed solvent of hexane and ethyl acetate to obtain 1-[5-(morpholin-4-ylcarbonyl)-4-(trifluoromethyl)pyrimidin-2-yl]-6-nitro-1,2,3,4-tetrahydroquinoline (62 mg) as a yellow powder.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)

Sources & evidence

ORD record
ord-f0ea5e30e98b4dc8ab90290c91886cbf
Source dataset
uspto-grants-2013_09
Patent number
US08524727B2

Reaction notes

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