Triethylamine → HCID 72551669, compound

HRID 749032Notes

Reaction equation

HRID 749032 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:29](=[O:33])[N:30]([CH3:32])[CH3:31])[CH2:10][C:11]1[CH:28]=[CH:27][C:14]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22][CH2:23][C:24]([OH:26])=O)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.Cl.[CH2:64]([O:71][NH2:72])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>CN(C=O)C.CCCCCC.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:29](=[O:33])[N:30]([CH3:32])[CH3:31])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22][CH2:23][C:24](=[O:26])[NH:72][O:71][CH2:64][C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)=[CH:27][CH:28]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 102312Benzyloxyamine hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69129073HCID 69129073, compound

Product 1

HCID 72551669HCID 72551669, compoundYield 98%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

The acid compound 62 (0.7 g, 1.533 mmol) was dissolved in dry DMF and cooled to 0-5° C. 1-Hydroxybenzotriazole (0.227 g, 1.686 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 0.293 g, 1.533 mmol), and triethylamine (0.641 mL, 4.59 mmol) were added to the above mixture followed by stirring for 15 min. O-Benzylhydroxylamine hydrochloride (0.269 g, 1.686 mmol) was added and the mixture was allowed to come to room temperature and stirred for 18 h. The solvent was evaporated under reduced pressure and the residual oil was taken up in EtOAc (100 mL). The organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×50 mL). The resulting EtOAc layer was dried and concentrated to yield the crude product. Flash chromatography (30-50% ethyl acetate in hexane containing 1% acetic acid) yielded the desired benzyl hydroxamate 63 (0.8 g, 98%). 1H NMR (400 MHz, DMSO-d6) 10.9 (s, 1H), 7.37-7.2 (m, 9H), 7.07 (t, J=7.2 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 6.76 (d, J=7.6 Hz, 1H), 4.71 (s, 2H), 4.54 (m, 1H), 2.89 (s, 3H), 2.81-2.72 (m, 7H), 2.49 (t, J=1.6 Hz, 2H), 1.30 (s, 9H).

Workup

  1. customto come to room temperature
  2. stirringstirred for 18 h
  3. customThe solvent was evaporated under reduced pressure
  4. extractionThe organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×50 mL)
  5. dry with materialThe resulting EtOAc layer was dried
  6. concentrationconcentrated
  7. customto yield the crude product

Sources & evidence

ORD record
ord-7c256eb4a65748e7a9b3a867242fc19e
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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