N-(tert-Butoxycarbonyl)-1,2-phenylenediamine → N-(2-t-butoxycarbonylaminophenyl)-4-(1-t-butoxycarbonylpiperidin-4-yl)benzamide

HRID 888023

Reaction equation

HRID 888023 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH2:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][CH:30]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C>[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:33](=[O:34])[C:32]1[CH:36]=[CH:37][C:29]([CH:26]2[CH2:27][CH2:28][N:23]([C:21]([O:20][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:22])[CH2:24][CH2:25]2)=[CH:30][CH:31]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 676311N-(tert-Butoxycarbonyl)-1,2-phenylenediamineHCID 224928594-(4-Carboxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68407604N-(2-t-butoxycarbonylaminophenyl)-4-(1-t-butoxycarbonylpiperidin-4-yl)benzamideYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(N-t-Butoxycarbonylamino)-2-aminobenzene (Method 17, 3.1 g, 14.7 mmol) was added to a stirred solution of 4-(1-t-butoxycarbonylpiperidin-4-yl)benzoic acid (4.1 g, 13.4 mmol) in DMF (50 ml) and the mixture stirred at ambient temperature for 10 minutes. 4-(4,6-dimethoxy-1,3,5-triazinyl-2-yl)-4-methylmorpholinium chloride (Method 18, 4.45 g, 16.1 mmol) was added and the mixture stirred at ambient temperature for 24 hours. The solvent was evaporated and the residue was dissolved in ethyl acetate (100 ml) and washed with water. The organics were dried over magnesium sulfate, filtered and evaporated. The resultant gum was purified by flash chromatography using 1% methanol/dichloromethane to give the title compound as a foam (5.44 g, 82%); NMR Spectrum: (DMSO-d6) 1.41 (s, 9H), 1.43 (s, 9H), 1.54 (m, 2H), 1.77 (m, 2H), 2.79 (m, 3H), 4.08 (m, 2H), 7.15 (m, 2H), 7.40 (d, 2H), 7.52 (m, 2H), 7.87 (d, 2H), 8.60 (br, 1H), 9.74 (br, 1H), Mass Spectrum: (M+H+-Boc) 396.

Workup

  1. stirringthe mixture stirred at ambient temperature for 24 hours
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in ethyl acetate (100 ml)
  4. washwashed with water
  5. dry with materialThe organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe resultant gum was purified by flash chromatography

Sources & evidence

ORD record
ord-65dcb7ef5848453993f43d82ccbb9135
Source dataset
uspto-grants-2012_08
Patent number
US08247562B2

Linked notes

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