Diethylether ethylacetate → Tert-butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate

HRID 222406Notes

Reaction equation

HRID 222406 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH2:25][CH2:26][N:27](C(OCC3C=CC=CC=3)=O)[CH2:28][CH:29]=2)=[CH:20][CH:19]=1)=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H].C(OCC)C.C(OCC)(=O)C>CO.[Pd]>[NH:27]1[CH2:28][CH2:29][CH:24]([C:21]2[CH:22]=[CH:23][C:18]([C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:17])=[CH:19][CH:20]=2)[CH2:25][CH2:26]1

Participants

6

Reactant 3

HCID 21584169Diethylether ethylacetateHCID 59830878benzyl 4-{4-[({2-[(tert-butoxycarbonyl)amino]phenyl}amino)carbonyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 59830875Tert-butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamateYield 81%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of benzyl 4-{4-[({2-[(tert-butoxycarbonyl)amino]phenyl}amino)carbonyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate (269 g, 524 mmol; prepared as described in Method 2 below) in methanol (3000 ml) was added 10% palladium on charcoal (10 g). The reaction mixture was placed under 5 bar pressure of hydrogen gas and heated to 50° C. for 1 h. The reaction mixture was cooled to room temperature, filtered through a pad of celite and the solvent evaporated under reduced pressure. The resultant foam was triturated under diethyl ether and filtered to give a white solid. This product was ground finely and stirred with 95:5 diethyl ether/ethyl acetate then collected by suction filtration. This solid was washed with diethyl ether, isohexane and dried in vacuo to afford the title compound (167 g, 81%); NMR Spectrum: (DMSO-d6) 1.45 (s, 9H), 1.57 (m, 2H), 1.72 (m, 2H), 2.61 (t, 2H), 2.69 (m, 1H), 3.07 (m, 2H), 7.18 (m, 2H), 7.40 (d, 2H), 7.53 (d, 2H), 7.91 (d, 2H), 8.70 (br s, 1H), 9.82 (br s, 1H); Mass Spectrum: M+H+396.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through a pad of celite
  3. customthe solvent evaporated under reduced pressure
  4. customThe resultant foam was triturated under diethyl ether
  5. filtrationfiltered
  6. customto give a white solid
  7. filtrationthen collected by suction filtration
  8. washThis solid was washed with diethyl ether, isohexane
  9. customdried in vacuo

Sources & evidence

ORD record
ord-99e7904ace954ceead67377416021f32
Source dataset
uspto-grants-2012_06
Patent number
US08207202B2

Reaction notes

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