Piperidine → HCID 72195769, compound

HRID 626347Notes

Reaction equation

HRID 626347 reaction equation
C1C=CC(P(C2C([C:24]3[C:33](P(C4C=CC=CC=4)C4C=CC=CC=4)=[CH:32][CH:31]=[C:30]4[C:25]=3[CH:26]=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]C2C=C(/C=C/C(OCC)=O)C=CC=2F)=[O:59])[C:51]2[C:56]([CH:57]=1)=[CH:55][CH:54]=[CH:53][CH:52]=2.BrC1C=[C:78]([C:86]([NH:88][C:89]2[CH:90]=[C:91](/C=C/C(OCC)=O)[CH:92]=[CH:93][CH:94]=2)=O)C2C(C=1)=CC=CC=2.N1[CH2:107][CH2:106][O:105]CC1.[NH:108]1[CH2:113][CH2:112]CCC1.CC(C)([O-:117])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>[N:88]1([C:89]2[CH:94]=[C:93]([C:48]3[CH:49]=[C:50]([C:58]([NH:60][C:33]4[CH:24]=[C:25](/[CH:26]=[CH:107]/[C:106]([OH:117])=[O:105])[CH:30]=[CH:31][CH:32]=4)=[O:59])[C:51]4[C:56]([CH:57]=3)=[CH:55][CH:54]=[CH:53][CH:52]=4)[CH:92]=[CH:91][CH:90]=2)[CH2:86][CH2:78][NH:108][CH2:113][CH2:112]1

Participants

10

Reactant 6

HCID 8082PiperidineHCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 90057937HCID 90057937, compoundHCID 90057966HCID 90057966, compound

Product 1

HCID 72195769HCID 72195769, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A Biotage Process Vial (5-20 mL) was charged with 4-7 mol % of (2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl) BINAP, 1-2 mol % of Pd2(dba)3, compound 15 or 23 (1 equivalent), morpholine or piperidine (2-5 equivalents), and potassium tertbutoxide (2-4 equivalents). The vial was charged with DMF (5-10 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 28 or 29. Purified material was obtained 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 28 or 29
  9. customPurified material was obtained by preparative HPLC

Sources & evidence

ORD record
ord-db0ffbe9fd6e48588781289a480d9d7f
Source dataset
uspto-grants-2016_04
Patent number
US09309187B2

Reaction notes

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