Piperidine → HCID 72195897, compound

HRID 626349Notes

Reaction equation

HRID 626349 reaction equation
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.Br[C:48]1[CH:49]=[C:50]([C:58]([NH:60][C:61]2[CH:62]=[C:63](/[CH:68]=[CH:69]/[C:70]([O:72]CC)=[O:71])[CH:64]=[CH:65][C:66]=2[F:67])=[O:59])[C:51]2[C:56]([CH:57]=1)=[CH:55][CH:54]=[CH:53][CH:52]=2.[NH:75]1[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]1.CC(C)([O-])C.[K+]>O.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].CN(C=O)C>[F:67][C:66]1[CH:65]=[CH:64][C:63](/[CH:68]=[CH:69]/[C:70]([OH:72])=[O:71])=[CH:62][C:61]=1[NH:60][C:58]([C:50]1[C:51]2[C:56](=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH:57]=[C:48]([N:75]2[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]2)[CH:49]=1)=[O:59]

Participants

8

Reactant 4

HCID 8082PiperidineHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 90057937HCID 90057937, compound

Product 1

HCID 72195897HCID 72195897, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A Biotage Process Vial (5-20 mL) was charged with BINAP (0.36 mmol), Pd2(dba)3 (0.18 mmol), ethyl(E)-3-[3-[(3-bromonaphthalene-1-carbonyl)amino]-4-fluoro-phenyl]prop-2-enoate (15) (1.81 mmol), piperidine (5.44 mmol), and potassium tertbutoxide (3.62 mmol). The vial was charged with DMF (5 mL) and irradiated at 100-130° C. for 1 h, using the microwave reactor Smith Synthesizer. After irradiation, the sample was cooled and diluted with water and extracted with ethyl acetate (3×50 mL). The organic layer was washed with water, brine and dried over Na2SO4 and the solvent evaporated to dryness to afford crude 29, which was purified by preparative HPLC.

Workup

  1. customirradiated at 100-130° C. for 1 h
  2. customAfter irradiation
  3. temperaturethe sample was cooled
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent evaporated to dryness
  8. customto afford crude 29, which
  9. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-58a1bcb39f6c48fa89c8aac5e15b789c
Source dataset
uspto-grants-2016_04
Patent number
US09309187B2

Reaction notes

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