1,1'-Carbonyldiimidazole → 5-(2-Tert-butoxycarbonylamino-phenylcarbamoyl)-thiophene-2-carboxylic acid methyl ester

HRID 1790214Notes

Reaction equation

HRID 1790214 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([C:22]([OH:24])=O)=[CH:20][CH:21]=1)=[O:16].[C:25]([O:29][C:30](=[O:39])[NH:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[NH2:38])([CH3:28])([CH3:27])[CH3:26]>C1COCC1>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([C:22](=[O:24])[NH:38][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[NH:31][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:39])=[CH:20][CH:21]=1)=[O:16]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 676311N-(tert-Butoxycarbonyl)-1,2-phenylenediamineHCID 8183525-(Methoxycarbonyl)thiophene-2-carboxylic acid

Product 1

HCID 581919625-(2-Tert-butoxycarbonylamino-phenylcarbamoyl)-thiophene-2-carboxylic acid methyl esterYield 80.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under an argon atmosphere 21.0 g (129 mmol) carbonyldiimidazol was added to a solution of 24.1 g (129 mmol) thiophene-2,5-dicarboxylic acid monomethyl ester in 600 ml THF. After 2 h at rt 26.9 g (129 mmol) (2-amino-phenyl)-carbamic acid tert-butyl ester were added and the reaction mixture was stirred for further 4 h at rt. The solvent was evaporated and the residue dissolved in 500 ml ethyl acetate. The organic phase was washed three times with 100 ml saturated aqueous NaHCO3 solution, twice with 80 ml water and was dried over sodium sulfate. The solvent was removed down to 80 ml when crystallization started. After 12 h the crystalls were filtered off and washed with little ice-cold t-butyl methyl ether and cold heptane. Drying under high vacuum yielded 38.9 g (103.4 mmol) 5-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-thiophene-2-carbox-ylic acid methyl ester, 1H-NMR (D6-DMSO) δ=1.45 (s, 9H), 3.87 (s, 3H), 7.14 (m, 1H), 7.22 (m, 1H), 7.46 (m,1H), 7.59 (m, 1H), 7.89 (m, 1H), 7.96 (m, 1H), 8.73 (br, 1H), 10.02 (s, 1H).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in 500 ml ethyl acetate
  3. washThe organic phase was washed three times with 100 ml saturated aqueous NaHCO3 solution
  4. dry with materialtwice with 80 ml water and was dried over sodium sulfate
  5. customThe solvent was removed down to 80 ml when crystallization
  6. filtrationAfter 12 h the crystalls were filtered off
  7. washwashed with little ice-cold t-butyl methyl ether and cold heptane
  8. customDrying under high vacuum

Sources & evidence

ORD record
ord-cc5fd901768f4887b9c9ef8595d7ca2c
Source dataset
uspto-grants-2006_07
Patent number
US07071219B2

Reaction notes

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