Acetic Acid → {1-Dimethylcarbamoyl-2-[4-(5-hydroxycarbamoyl-pyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 273440Notes

Reaction equation

HRID 273440 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:27](=[O:31])[N:28]([CH3:30])[CH3:29])[CH2:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][N:17]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.Cl.[NH2:40][OH:41].C(O)(=O)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:27](=[O:31])[N:28]([CH3:29])[CH3:30])[CH2:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](=[O:22])[NH:40][OH:41])=[CH:18][N:17]=2)=[CH:13][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 79724-MethylmorpholineHCID 443297Hydroxyamine hydrochlorideHCID 691138456-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-nicotinic acid

Product 1

HCID 72575122{1-Dimethylcarbamoyl-2-[4-(5-hydroxycarbamoyl-pyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The acid compound 19 (1.0 g, 2.328 mmol) was dissolved in dry DMF and stirred under an atmosphere of argon. N-Methylmorpholine (1.02 mL, 9.32 mmol) was added. After 20 min, hydroxylamine hydrochloride (0.323 g, 4.66 mmol) was added and the reaction mixture was warmed up to room temperature and stirred overnight. The solvent was removed under reduced pressure and residual material was partitioned between EtOAc (50 mL) and saturated NH4Cl solution (1×30 mL). The organic layer was dried and concentrated to yield the crude material. Flash chromatography on SiO2 gel using hexanes-ethyl acetate (70-60%) mixture containing 1% acetic acid furnished the desired hydroxamic acid compound 20 (0.5 g, 98%) 1H NMR (400 MHz, DMSO-d6): 8.47 (br, 1H) 8.14 (dd, J=8.8 and 2.4 Hz, 1H), 7.29 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.8 Hz, 1H), 7.05 (m, 3H), 4.56 (m, 1H), 2.93 (s, 3H) 2.85-2.75 (m, 2H), 2.79 (s, 3H), 1.32 (s, 9H)

Workup

  1. stirringstirred overnight
  2. customThe solvent was removed under reduced pressure and residual material
  3. customwas partitioned between EtOAc (50 mL) and saturated NH4Cl solution (1×30 mL)
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customto yield the crude material

Sources & evidence

ORD record
ord-ee5a02531ee045ab9dbffc53d7c2aed7
Source dataset
uspto-grants-2008_11
Patent number
US07456292B2

Reaction notes

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