4-Methylmorpholine → HCID 72575119, compound

HRID 273428Notes

Reaction equation

HRID 273428 reaction equation
[CH2:1]([O:8][C:9]([CH:11]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:12][C:13]1[CH:28]=[CH:27][C:16]([O:17][C:18]2[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=2)=[CH:15][CH:14]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.CN([P+]([O:54][N:55]1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.Cl.NO>CN(C)C=O.C(O)(=O)C>[CH2:1]([O:8][C:9](=[O:10])[CH:11]([NH:29][C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([O:17][C:18]2[CH:19]=[CH:20][C:21]([C:22](=[O:23])[NH:55][OH:54])=[CH:25][CH:26]=2)=[CH:27][CH:28]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 443297Hydroxyamine hydrochlorideHCID 69109367HCID 69109367, compound

Product 1

HCID 72575119HCID 72575119, compoundYield 44.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Acid compound 4 (1.1 g, 2.24 mmol) was dissolved in N,N-dimethylformamide (10 mL) and stirred under an atmosphere of argon. N-Methylmorpholine (1.0 mL, 8.96 mmol) was added, the reaction mixture was cooled to 0° C. and BOP reagent (1.09 g, 2.46 mmol) was added. After 20 min, hydroxylamine hydrochloride (0.31 g, 4.48 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 (1:1) mixture containing 1% acetic acid furnished the desired hydroxamic acid compound 5 (0.5 g, 44%). 1H NMR (DMSO-d6): 11.20 (br, 1H), 9.00 (br, 1H), 7.76 (d, J=8.8 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 7.28-7.38 (m, 7H), 6.98 (overlapped d, J=8.4 Hz, 4H), 5.12 (s, 2H), 4.21-4.27 (m, 1H), 3.03 (dd, J=13.6 and 5.6 Hz, 1H), 2.89 (dd, J=10.0 and 14.0 Hz, 1H), 1.33 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-37e26859e0124039901ee9d4f03d47c1
Source dataset
uspto-grants-2008_11
Patent number
US07456292B2

Reaction notes

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