p-(Trifluoromethoxy)phenyl isocyanate → 1-(1-(2-Methylbutanoyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

HRID 574687Notes

Reaction equation

HRID 574687 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]=[C:11]=[O:12])=[CH:6][CH:5]=1.[NH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22](=[O:27])[CH:23]([CH3:26])[CH2:24][CH3:25])[CH2:18][CH2:17]1>C(Cl)Cl>[CH3:26][CH:23]([CH2:24][CH3:25])[C:22]([N:19]1[CH2:18][CH2:17][CH:16]([NH:15][C:11]([NH:10][C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:13])([F:14])[F:1])=[CH:9][CH:8]=2)=[O:12])[CH2:21][CH2:20]1)=[O:27]

Participants

4

Reactant 2

HCID 92298p-(Trifluoromethoxy)phenyl isocyanateHCID 167829341-(4-Amino-1-piperidinyl)-2-methyl-1-butanone

Product 1

HCID 716801971-(1-(2-Methylbutanoyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)ureaYield 895.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-(Trifluoromethoxy)phenylisocyanate (100 mg, 0.49 mmol) and 1-(4-aminopiperidin-1-yl)-2-methylbutan-1-one (90 mg, 0.49 mmol) was dissolved in CH2Cl2 (100 mL) and stirred for 12 h. The reaction was quenched by addition of water. The organic layer was isolated and the aqueous layer was extracted with EtOAc for 4 times. The combined organic layer was concentrated under vacuo and was further purified by flash chromatography (EtOAc:Hex/1:1) yielding final product (168 mg, 4.39 mmol, 89%). H-NMR (DMSO-d6) ∂ 0.80 (m, 3H), 0.97 (m, 3H), 1.28 (m, 3H), 1.53 (m, 1H), 1.85 (tbr, 2H), 2.71 (m, 1H), 2.78 (m, 1H), 3.16 (t, J=12 Hz, 1H), 3.71 (m, 1H), 3.88 (d, J=12 Hz, 1H), 4.21 (br, 1H), 6.26 (tbr, 1H), 7.22 (d, J=9 Hz, 2H), 7.47 (d, J=9 Hz, 2H), 8.55 (d, J=9 Hz, 2H).

Workup

  1. customThe reaction was quenched by addition of water
  2. customThe organic layer was isolated
  3. extractionthe aqueous layer was extracted with EtOAc for 4 times
  4. concentrationThe combined organic layer was concentrated under vacuo
  5. customwas further purified by flash chromatography (EtOAc:Hex/1:1)

Sources & evidence

ORD record
ord-25852ef2c42d4877aea51b13bd09e158
Source dataset
uspto-grants-2015_05
Patent number
US09034903B2

Reaction notes

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