Cesium carbonate → HCID 86708475, compound

HRID 1430794Notes

Reaction equation

HRID 1430794 reaction equation
Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].[N:71]1([C:77]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])=[O:78])[CH2:76][CH2:75][NH:74][CH2:73][CH2:72]1>C1(C)C=CC=CC=1.C(OCC)(=O)C.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]>[C:13]([O:12][C:11]([NH:10][C:4]1[C:3]([Cl:18])=[C:2]([N:74]2[CH2:73][CH2:72][N:71]([C:77]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])=[O:78])[CH2:76][CH2:75]2)[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=1)=[O:17])([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate2×

Product 1

HCID 86708475HCID 86708475, compoundYield 50.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

(I11A): Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (Intermediate 1) (4.5 g, 13.57 mmol), Pd2 dba3 (0.746 g, 0.814 mmol), BINAP (0.676 g, 1.086 mmol) and Cs2CO3 (8.84 g, 27.1 mmol) were suspended in toluene (12.0 mL) at room temperature. Tert-butyl piperazine-1-carboxylate (3.29 g, 17.64 mmol) was added and the reaction was degassed and purged with Argon, degassed for 6 times. The reaction mixture was heated at 105° C. for overnight. On completion of the reaction, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, filtered through celite and concentrated. The Crude material was purified by column chromatography (ISCO), using 0-10% ethyl acetate-hexane as eluent. Pure fractions were concentrated to obtain tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)piperazine-1-carboxylate (3.0 g) as an off-white solid.

Workup

  1. customthe reaction was degassed
  2. custompurged with Argon
  3. customdegassed for 6 times
  4. customOn completion of the reaction
  5. temperaturethe reaction mixture was cooled to room temperature
  6. filtrationfiltered through celite
  7. concentrationconcentrated
  8. customThe Crude material was purified by column chromatography (ISCO)
  9. concentrationPure fractions were concentrated

Sources & evidence

ORD record
ord-a9c18c687e40436ca7e48c82531380fa
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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