Dimethylformamide → 4-{4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyrylamino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 511123Notes

Reaction equation

HRID 511123 reaction equation
[Li+].F[C:3](F)(F)[C:4]1[CH:9]=CC(N2CCN(CCCC([O-])=O)CC2)=C[CH:5]=1.F[P-](F)(F)(F)(F)F.CN(C)C([O:37]N1C2C=CC=CC=2N=N1)=[N+](C)C.[N+](C1C=CC(N2C[CH2:61][CH:60]([NH:63][C:64](=[O:84])[CH2:65][CH2:66][CH2:67][N:68]3[CH2:73][CH2:72][N:71]([C:74]4[CH:79]=[CH:78][C:77]([C:80]([F:83])([F:82])[F:81])=[CH:76][CH:75]=4)[CH2:70][CH2:69]3)[CH2:59]C2)=CC=1C(F)(F)F)([O-])=O.C(N(C(C)C)CC)(C)C.[CH3:98][N:99]([CH3:102])[CH:100]=[O:101]>C(OC(=O)C)C.O1CCCC1>[C:4]([O:101][C:100]([N:99]1[CH2:102][CH2:61][CH:60]([NH:63][C:64](=[O:84])[CH2:65][CH2:66][CH2:67][N:68]2[CH2:73][CH2:72][N:71]([C:74]3[CH:79]=[CH:78][C:77]([C:80]([F:83])([F:81])[F:82])=[CH:76][CH:75]=3)[CH2:70][CH2:69]2)[CH2:59][CH2:98]1)=[O:37])([CH3:9])([CH3:5])[CH3:3]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585760704-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium saltHCID 58576694N-[1-(4-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl]-4-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-butyramide2×

Product 1

HCID 585766414-{4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyrylamino}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (425 mg; 1.32 mmol, prepared in accordance with Example 3) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (500 mg; 1.32 mmol) are diluted in a 5 to 1 mixture of dimethylformamide and tetrahydrofuran (6 mL) and the resulting solution is stirred for 5 minutes. 4-Amino-piperidine-1-carboxylic acid tert-butyl ester (264 mg; 1.32 mmol, free base of Example 73) and diisopropylethyl amine (460 μL; 2.64 mmol) are added and the reaction is then stirred for 90 minutes at room temperature. Following dilution with ethylacetate (30 mL), the organic layer is washed with aq. sat. sodium hydrogen carbonate (3×10 mL), is dried over magnesium sulfate and concentrated under reduced pressure to afford the desired product (660 mg; 1.32 mmol).

Workup

  1. stirringthe reaction is then stirred for 90 minutes at room temperature
  2. washthe organic layer is washed with aq. sat. sodium hydrogen carbonate (3×10 mL)
  3. dry with materialis dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-be0038d5de9f423fa4f37813b07fa2d7
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

Loading…