Dicyclohexylcarbodiimide → 4-Tert-butoxycarbonylamino-1-methyl-1h-pyrrole-2-carboxylic acid benzotriazol-1yl ester

HRID 1268367Notes

Reaction equation

HRID 1268367 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([C:15]([OH:17])=[O:16])[N:12]([CH3:14])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:18]1[CH:19]=[CH:20][C:21]2[N:26](O)[N:25]=[N:24][C:22]=2[CH:23]=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([C:15]([O:17][N:24]2[C:22]3[CH:23]=[CH:18][CH:19]=[CH:20][C:21]=3[N:26]=[N:25]2)=[O:16])[N:12]([CH3:14])[CH:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 27356364-[(tert-Butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid

Product 1

HCID 27559874-Tert-butoxycarbonylamino-1-methyl-1h-pyrrole-2-carboxylic acid benzotriazol-1yl esterYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Boc-Py-acid, 4-[(tert-Butoxycarbonyl)amino]-1-methylpyrrole-2-carboxylic acid (31 g, 129 mmol) was dissolved in 500 mL DMF, HOBt (17.4 g, 129 mmol) was added followed by DCC (34 g, 129 mmol). The reaction was stirred for 24 h and then filtered dropwise into a well stirred solution of 5 L of ice water. The precipitate was allowed to sit for 15 min at 0° C. and then collected by filtration. The wet cake was dissolved in 500 mL DCM, and the organic layer added slowly to a stirred solution of cold petroleum ether (4° C.). The mixture was allowed to stand at −20° C. for 4 h and then collected by vacuum filtration and dried in vacuo to provide (39 g, 85% yield) of 1,2,3-Benzotriazol-1-yl 4-[(tert-butoxycarbonyl)-amino]-1-methylpyrrole-2-carboxylate as a finely divided white powder. TLC (7:2 benzene/ethyl acetate v/v) Rf 0.6, 1H NMR (DMSO-d6) δ9.43 (s, 1H) , 8.12 (d, 1H, J=8.4 Hz), 7.80 (d, 1H, J=8.2Hz), 7.64 (t, 1H, J=7.0 Hz), 7.51 (m, 2H), 7.18 (s, 1H), 3.83 (s, 3H), 1.45 (s, 9H) , 13C NMR (DMSO-d6) δ156.5, 153.3, 143.2, 129.6, 129.2, 125.7, 125.2, 124.6, 120.3, 112.8, 110.3, 109.8, 79.5, 36.8, 28.6.; IR (KBr) 3246, 3095, 2979, 1764, 1711, 1588, 1389, 1365, 1274, 1227, 1160, 1101, 999, 824, 748.; FABMS mle 358.152 (M+H 358.151 calc. for C17H20N5O4)

Workup

  1. filtrationfiltered dropwise into a well
  2. stirringstirred solution of 5 L of ice water
  3. waitto sit for 15 min at 0° C.
  4. filtrationcollected by filtration
  5. dissolutionThe wet cake was dissolved in 500 mL DCM
  6. additionthe organic layer added slowly to a stirred solution of cold petroleum ether (4° C.)
  7. waitto stand at −20° C. for 4 h
  8. filtrationcollected by vacuum filtration
  9. customdried in vacuo

Sources & evidence

ORD record
ord-876c3577f08c402daff43573f9618480
Source dataset
uspto-grants-2003_04
Patent number
US06555692B1

Reaction notes

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