Ethyl 4-piperidinecarboxylate → HCID 66697232, compound

HRID 2096747Notes

Reaction equation

HRID 2096747 reaction equation
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.Br[C:48]1[CH:53]=[CH:52][C:51]([CH:54]([CH3:73])[C:55]([C:61]2[CH:62]=[CH:63][C:64]3[O:69][CH2:68][C:67](=[O:70])[N:66]([CH3:71])[C:65]=3[CH:72]=2)([OH:60])[C:56]([F:59])([F:58])[F:57])=[C:50]([Cl:74])[CH:49]=1.[NH:75]1[CH2:80][CH2:79][CH:78]([C:81]([O:83][CH2:84][CH3:85])=[O:82])[CH2:77][CH2:76]1>C1(C)C=CC=CC=1.CCOC(C)=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]>[CH2:84]([O:83][C:81]([CH:78]1[CH2:79][CH2:80][N:75]([C:48]2[CH:53]=[CH:52][C:51]([CH:54]([CH3:73])[C:55]([OH:60])([C:61]3[CH:62]=[CH:63][C:64]4[O:69][CH2:68][C:67](=[O:70])[N:66]([CH3:71])[C:65]=4[CH:72]=3)[C:56]([F:59])([F:58])[F:57])=[C:50]([Cl:74])[CH:49]=2)[CH2:76][CH2:77]1)=[O:82])[CH3:85]

Participants

7

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylate2×HCID 634876Binap, (A+-)-2×HCID 666971866-[2-(4-Bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-4-methyl-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 66697232HCID 66697232, compoundYield 3.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 2,2′-bis(diphenylphosphino)-1,1′binaphthyl (3.1 mg), tris(dibenzylideneacetone)dipalladium (0) (1.5 mg) and sodium-tert.-butylate (19 mg) in toluene (15 ml) were added 6-[2-(4-bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-4-methyl-4H-benzo[1,4]oxazin-3-one (Example 22, step 3, 80 mg) and ethyl piperidine-4-carboxylate (29 mg). The mixture was stirred at room temperature overnight. 2,2′-Bis(diphenylphosphino)-1,1′binaphthyl (3.1 mg), ethyl piperidine-4-carboxylate (29 mg) and tris(dibenzylideneacetone)dipalladium (0) (1.5 mg) were added and the mixture was stirred at 80° C. for 4 h. After cooling to room temperature, the mixture was diluted with EtOAc. The organic phase was washed with water, dried (MgSO4), filtered and concentrated to dryness. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>4:1) to give the title compound (3 mg) as light yellow oil. MS (m/e)=555.3 [M+H+].

Workup

  1. stirringthe mixture was stirred at 80° C. for 4 h
  2. temperatureAfter cooling to room temperature
  3. washThe organic phase was washed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>4:1)

Sources & evidence

ORD record
ord-d8e4b7762e3d4ca098cbe25f8a51b1f6
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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