3-Aminophenyl dimethylcarbamate → Tert-butyl 4-(tert-butoxycarbonylamino)-4-(3-(dimethylcarbamoyloxy)phenylcarbamoyl)piperidine-1-carboxylate

HRID 216090Notes

Reaction equation

HRID 216090 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C:9]1([C:22](O)=[O:23])[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)=[O:7])([CH3:4])[CH3:3].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.[CH3:58][N:59]([CH3:70])[C:60](=[O:69])[O:61][C:62]1[CH:67]=[CH:66][CH:65]=[C:64]([NH2:68])[CH:63]=1>C(OC(C)C)(=O)C.CCOC(C)=O>[C:2]([O:5][C:6]([NH:8][C:9]1([C:22](=[O:23])[NH:68][C:64]2[CH:65]=[CH:66][CH:67]=[C:62]([O:61][C:60](=[O:69])[N:59]([CH3:70])[CH3:58])[CH:63]=2)[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]1)=[O:7])([CH3:4])([CH3:3])[CH3:1]

Participants

7

Reactant 4

HCID 298773-Aminophenyl dimethylcarbamateHCID 81531DiisopropylethylamineHCID 12682251-(tert-Butoxycarbonyl)-4-((tert-butoxycarbonyl)amino)piperidine-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 68992221Tert-butyl 4-(tert-butoxycarbonylamino)-4-(3-(dimethylcarbamoyloxy)phenylcarbamoyl)piperidine-1-carboxylateYield 45%

Reagents, catalysts & solvents 2

HCID 7915Isopropyl AcetateSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Boc-amino-(4-N-Boc-piperidinyl)carboxylic acid (0.114 g, 0.33 mmol), HATU (0.151 g, 0.40 mmol) and N,N-diisopropylethylamine (128 mg, 1.0 mmol) were combined in isopropyl acetate (2.3 mL) and stirred at room temperature for 15 minutes. 3-aminophenyl dimethylcarbamate (0.072 g, 0.40 mmol) was added, and the mixture heated at 80° C. for 1.5 hours. The reaction mixture was allowed to cool, diluted with EtOAc, washed with 2 N Na2CO3, 1 N HCl, and brine, and then dried over MgSO4 and concentrated. Purification by silica gel chromatography (60% EtOAc/hexanes) gave the title compound (0.075 g, 45%) as a white solid. MS (ES+) [M+NH4]+=524.

Workup

  1. temperaturethe mixture heated at 80° C. for 1.5 hours
  2. temperatureto cool
  3. washwashed with 2 N Na2CO3, 1 N HCl, and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-77092528ceab4c01a1aafa2b79b8c6da
Source dataset
uspto-grants-2012_06
Patent number
US08193202B2

Reaction notes

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