Binap, (A+-)- → 4-(4-Trifluoromethylsulfanyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 511097Notes

Reaction equation

HRID 511097 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.CC(C)([O-])C.[Na+].Br[C:54]1[CH:59]=[CH:58][C:57]([S:60][C:61]([F:64])([F:63])[F:62])=[CH:56][CH:55]=1.[C:65]([O:69][C:70]([N:72]1[CH2:77][CH2:76][CH:75]([NH2:78])[CH2:74][CH2:73]1)=[O:71])([CH3:68])([CH3:67])[CH3:66]>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:65]([O:69][C:70]([N:72]1[CH2:77][CH2:76][CH:75]([NH:78][C:54]2[CH:59]=[CH:58][C:57]([S:60][C:61]([F:64])([F:63])[F:62])=[CH:56][CH:55]=2)[CH2:74][CH2:73]1)=[O:71])([CH3:68])([CH3:66])[CH3:67]

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 7364134-(Trifluoromethylthio)bromobenzeneHCID 12682914-Amino-1-Boc-piperidineHCID 23676156Sodium t-butoxide

Product 1

HCID 585766104-(4-Trifluoromethylsulfanyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl esterYield 48.4%

Reagents, catalysts & solvents 3

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

Procedure

Tris(dibenzylideneacetone)dipalladium (23 mg; 0.03 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (46 mg; 0.07 mmol), sodium tert-butoxide (176 mg; 1.83 mmol), 1-bromo-4-trifluoromethylsulfanyl-benzene (314 mg; 1.22 mmol) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (302 mg; 1.51 mmol) are suspended in dry toluene (5 mL) and the mixture is irradiated in a mono-mode microwave oven for 20 minutes at 120° C. The mixture is then cooled down to room temperature, is diluted with ethyl acetate (15 mL), filtered and concentrated under reduced pressure. The crude residue is then diluted in dichloromethane (15 mL) and filtered over a short silica gel pad. The desired product is eluted from the silica gel pad with dichloromethane and the fractions of interest are concentred under reduced pressure to afford the desired product (220 mg; 0.59 mmol).

Workup

  1. customthe mixture is irradiated in a mono-mode microwave oven for 20 minutes at 120° C
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. additionThe crude residue is then diluted in dichloromethane (15 mL)
  5. filtrationfiltered over a short silica gel pad
  6. washThe desired product is eluted from the silica gel pad with dichloromethane

Sources & evidence

ORD record
ord-088467c7119d41ed861d7f7dbcd5335f
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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