3-Aminophenyl dimethylcarbamate → tert-butyl 4-(3-(dimethylcarbamoyloxy)-phenylcarbamoyl)-4-((1-trityl-1H-imidazol-4-yl)methyl)piperidine-1-carboxylate

HRID 216079Notes

Reaction equation

HRID 216079 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[N:19]=[CH:20][N:21]([C:23]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:22]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH3:75][N:76]([CH3:87])[C:77](=[O:86])[O:78][C:79]1[CH:84]=[CH:83][CH:82]=[C:81]([NH2:85])[CH:80]=1>C(OC(C)C)(=O)C.CCOC(C)=O>[CH3:75][N:76]([CH3:87])[C:77]([O:78][C:79]1[CH:80]=[C:81]([NH:85][C:14]([C:11]2([CH2:17][C:18]3[N:19]=[CH:20][N:21]([C:23]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:22]=3)[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10]2)=[O:15])[CH:82]=[CH:83][CH:84]=1)=[O:86]

Participants

7

Reactant 4

HCID 298773-Aminophenyl dimethylcarbamateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 689935991-(tert-butoxycarbonyl)-4-((1-trityl-1H-imidazol-4-yl)methyl)piperidine-4-carboxylic acid

Product 1

HCID 68992070tert-butyl 4-(3-(dimethylcarbamoyloxy)-phenylcarbamoyl)-4-((1-trityl-1H-imidazol-4-yl)methyl)piperidine-1-carboxylateYield 43.2%

Reagents, catalysts & solvents 2

HCID 7915Isopropyl AcetateSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 1-(tert-butoxycarbonyl)-4-((1-trityl-1H-imidazol-4-yl)methyl)piperidine-4-carboxylic acid from step B (270 mg, 0.6 mmol) in isopropyl acetate (5 mL) were added HATU (273 mg, 0.73 mmol) and N,N-diisopropylethylamine (205 μL, 1.2 mmol). The mixture was stirred for 5 min, and 3-aminophenyl dimethylcarbamate (108 mg, 0.6 mmol) was added. The resulting mixture was heated at 90° C. for 2 hours. The reaction mixture was diluted with EtOAc (10 mL), washed with aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography (10-70% EtOAc:Hexanes) to afford the title compound (185 mg, 43%). MS (ES+) [M+H]+=714.2.

Workup

  1. washwashed with aqueous NaHCO3 and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by silica gel chromatography (10-70% EtOAc:Hexanes)

Sources & evidence

ORD record
ord-0b172d079e5340998287b79a5bd3d22d
Source dataset
uspto-grants-2012_06
Patent number
US08193202B2

Reaction notes

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