Binap, (A+-)- → (2R,4S)-4-[5-(4-Tert-butoxycarbonylbutoxy)pyrimidin-2-yl-amino]-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline

HRID 661450Notes

Reaction equation

HRID 661450 reaction equation
[C:1]([O:5][C:6](=[O:19])[CH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[N:14][C:15](Cl)=[N:16][CH:17]=1)([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:66]([C@@H:68]1[CH2:77][C@H:76]([NH2:78])[C:75]2[C:70](=[CH:71][CH:72]=[C:73]([C:79]([F:82])([F:81])[F:80])[CH:74]=2)[NH:69]1)[CH3:67].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[C:1]([O:5][C:6]([CH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[N:14][C:15]([NH:78][C@@H:76]2[C:75]3[C:70](=[CH:71][CH:72]=[C:73]([C:79]([F:82])([F:80])[F:81])[CH:74]=3)[NH:69][C@H:68]([CH2:66][CH3:67])[CH2:77]2)=[N:16][CH:17]=1)=[O:19])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 24969672(2R,4S)-2-Ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinolin-4-ylamineHCID 866365415-(2-Chloropyrimidin-5-yloxy)valeric acid tert-butyl ester

Product 1

HCID 67140966(2R,4S)-4-[5-(4-Tert-butoxycarbonylbutoxy)pyrimidin-2-yl-amino]-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

5-(2-Chloropyrimidine-5-yloxy)-pentanoic acid tert-butyl ester (464 mg), palladium acetate (26 mg), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (81 mg) were dissolved in toluene (0.5 ml) and the mixture was stirred under nitrogen atmosphere at 50° C. for an hour. The reaction mixture was cooled to room temperature, thereto was added the compound obtained in Example 4 (1) dissolved in toluene (9.5 ml) and stirred at room temperature for 15 minutes. Then, sodium tert-butoxide (310 mg) was added and the mixture was stirred at room temperature for 4 days. Water and ethyl acetate was added to the mixture and the organic layer was separated, washed with a saturated brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=49:1→17:3→4:1) to give the titled compound (537 mg). MS (m/z): 495 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringstirred at room temperature for 15 minutes
  3. stirringthe mixture was stirred at room temperature for 4 days
  4. customthe organic layer was separated
  5. washwashed with a saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=49:1→17:3→4:1)

Sources & evidence

ORD record
ord-566860464dff4554ad56d913c932036d
Source dataset
uspto-grants-2011_12
Patent number
US08084611B2

Reaction notes

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