Ammonium Chloride → HCID 66869519, compound

HRID 1992657Notes

Reaction equation

HRID 1992657 reaction equation
CC(C)([O-])C.[Na+].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.[C:53]([O:57][C:58](=[O:71])[CH2:59][C:60]1[C:65]([C:66]([F:69])([F:68])[F:67])=[CH:64][N:63]=[C:62](Cl)[CH:61]=1)([CH3:56])([CH3:55])[CH3:54].[CH3:72][N:73]1[CH2:78][CH2:77][NH:76][CH2:75][CH2:74]1.[NH4+].[Cl-]>O1CCOCC1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:53]([O:57][C:58](=[O:71])[CH2:59][C:60]1[C:65]([C:66]([F:69])([F:68])[F:67])=[CH:64][N:63]=[C:62]([N:76]2[CH2:77][CH2:78][N:73]([CH3:72])[CH2:74][CH2:75]2)[CH:61]=1)([CH3:56])([CH3:55])[CH3:54]

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 531671-MethylpiperazineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86623477HCID 86623477, compound

Product 1

HCID 66869519HCID 66869519, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Sodium tert-butoxide (354 mg, 3.68 mmol) is dried under high vacuum at approximately 80° C. After purging with argon and cooling to RT, palladium acetate (60 mg, 0.27 mmol), rac-2,2′-bis-diphenylphosphanyl-[1,1]binaphthalenyl (rac-BINAP, 83 mg, 0.13 mmol) and (2-chloro-5-trifluoromethyl-pyridin-4-yl)-acetic acid tert-butyl ester (990 mg, 3.35 mmol) are added. The mixture is dissolved in dioxane (11 ml, degassed with three freeze-thaw cycles under HV/argon), and 1-methyl-piperazine (369 mg, 3.68 mmol) is added. The round bottom flask containing the reaction mixture is immersed into a pre-heated oil bath (T=85° C.). After 1 h, TLC analysis indicated almost complete conversion of starting materials. The reaction mixture is cooled to RT, diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. The organic layer is separated, washed with brine, dried over Na2SO4, and the solvent is evaporated. The residue is purified by FCC (CH2Cl2/MeOH, slow gradient from 99:1 to 94:6) to afford the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.44 (s, 9H), 2.34 (s, 3H), 2.50 (m, 4H), 3.59 (s, 2H), 3.66 (m, 4H), 6.54 (s, 1H), 8.35 (s, 1H). ES+−MS: 360.3 [M+H]+.

Workup

  1. customAfter purging with argon
  2. additionThe round bottom flask containing the reaction mixture
  3. customis immersed into a pre-heated oil bath
  4. custom(T=85° C.)
  5. temperatureThe reaction mixture is cooled to RT
  6. customThe organic layer is separated
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. customthe solvent is evaporated
  10. customThe residue is purified by FCC (CH2Cl2/MeOH, slow gradient from 99:1 to 94:6)

Sources & evidence

ORD record
ord-fb7cbd792f4f4f9f962889dabe7be011
Source dataset
uspto-grants-2010_01
Patent number
US07648989B2

Reaction notes

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