Dicyclohexylcarbodiimide → HCID 86609300, compound

HRID 33998Notes

Reaction equation

HRID 33998 reaction equation
[CH2:1]1[CH2:6][CH2:5][CH:4]([N:7]=[C:8]=NC2CCCCC2)CC1.[C:16]1(/[CH:22]=[CH:23]/[CH2:24][O:25][C:26]([NH:28][C:29]2[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=2[C:31]([OH:33])=O)=[O:27])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1C=CC2N([OH:47])N=NC=2C=1>C(Cl)Cl.CN(C=O)C>[C:16]1(/[CH:22]=[CH:23]/[CH2:24][O:25][C:26](=[O:27])[NH:28][C:29]2[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=2[C:31]([N:7]2[CH2:4][CH2:5][CH:6]([CH2:1][OH:47])[CH2:8]2)=[O:33])[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 587576422-((E)-3-phenyl-allyloxycarbonylamino)-benzoic acid

Product 1

HCID 86609300HCID 86609300, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-5 °C

Procedure

A solution of DCC (4.54 g, 22 mmol) dissolved in the minimum of CH2Cl2 was added dropwise to compound 73 (6 g, 0.020 mol) in CH2Cl2 at −5C, whilst stirring, with a catalytic amount of DMF (10 drops). The reaction mixture was stirred for a further five minutes before HOBt (3.0 g, 22 mmol) in CH2Cl2 was added. The reaction mixture was allowed to stir for 1 hour at −5° C., then left to stir for 12 hours at room temperature. The colourless precipitate of DCU was removed by filtration and the remaining reaction mixture cooled to −5° C. (S)-pyrrolidinemethanol (2.37 mL, 24 mmol) was added and the reaction mixture allowed to warm to room temperature and, stirred for 12 hours. TLC (70% Pet ether/EtOAc) revealed reaction completion. The reaction mixture was washed with NaHCO3 (4×100 mL), NH4Cl (4×100 mL), H2O (4×100 mL), brine (4×100 mL) and dried over MgSO4. Purification was achieved via flash column chromatography (60% pet ether/EtOAc) to furnish compound 74 as a stiff brown oil (95%). 1H NMR (250 MHz, CDCl3); δ 8.69 (s, 1H, NH), 8.13 (d, 1H, J=8.2 Hz, aromatic H), 7.42-7.22 (m, 6H, Coc aromatic H and aromatic H), 7.06 (ddd, 1H, J=1.07, 7.6, 7.5, aromatic H), 6.70 (d, 1H, J=16 Hz, 3′-H), 6.34 (dt, 1H, J=6.4, 18 Hz, 2′-H), 4.81 (dd, 2H, J=1.1, 6.4, 1′-H), 4.40 (br, s, 1H, H-11a), 3.85-3.42 (m, 4H, H-11, H-3), 2.06-1.70 (m, 4H, 1-H, H-2); 13C NMR (62.9 MHz, CDCl3) δ 171.3 (ester carbonyl), 136.6 (aromatic quat), 134.6 (methine), 131.3 (methine), 129.0 (methine), 128.5 (methine), 128.0 (methine), 127.1 (methine), 123.9 (alkenic methine), 122.7 (methine), 121.3 (methine), 67.0 (Coc, C-1), 66.2 (methylene Coc), 61.1 (methine, C-11a), 51.9 (methine, C-3), 28.8 (methine, C-1), 25.5 (methine, C-2); MS m/z; 381 (M+. +1), 363, 337, 308, 279, 261, 247, 229, 203, 117.

Workup

  1. additionwas added
  2. waitleft
  3. stirringto stir for 12 hours at room temperature
  4. customThe colourless precipitate of DCU was removed by filtration
  5. customthe remaining reaction mixture
  6. additionwas added
  7. temperatureto warm to room temperature
  8. stirringstirred for 12 hours
  9. customreaction completion
  10. washThe reaction mixture was washed with NaHCO3 (4×100 mL), NH4Cl (4×100 mL), H2O (4×100 mL), brine (4×100 mL)
  11. dry with materialdried over MgSO4
  12. customPurification

Sources & evidence

ORD record
ord-704ddb77a76a4e87b3404363b011b7ab
Source dataset
uspto-grants-2008_09
Patent number
US07429658B2

Reaction notes

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