4-Methylmorpholine → HCID 72575117, compound

HRID 273435Notes

Reaction equation

HRID 273435 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][CH:17]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.CN([P+]([O:49][N:50]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(Cl)(Cl)Cl.CO>[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:12]=[CH:13][C:14]([O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](=[O:22])[NH:50][OH:49])=[CH:18][CH:17]=2)=[CH:25][CH:26]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 443297Hydroxyamine hydrochlorideHCID 69205989HCID 69205989, compound

Product 1

HCID 72575117HCID 72575117, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

Acid compound 11 (1.9 g, 4.43 mmol) was dissolved in N,N-dimethylformamide (20 mL) and stirred under an atmosphere of argon. N-Methylmorpholine (1.95 mL, 18.0 mmol) was added, the reaction mixture was cooled to 0° C. and BOP reagent (2.16 g, 4.88 mmol) was added. After 20 min, hydroxylamine hydrochloride (0.62 g, 8.87 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 over silica gel using chloroform-methanol (19:1) yielded the desired hydroxamic acid compound 12 (0.9 g, 46%). 1H NMR (DMSO-d6): 8.95 (br, 1H), 7.73 (d, J=9.2 Hz, 2H), 7.28 (d, J=8.4 Hz, 2H), 7.18 (d, J=8.4 Hz, 1H), 7.00 (d, J=8.8 Hz, 2H), 6.95 (d, J=8.8 Hz, 2H), 4.55 (m, 1H), 2.91 (s, 3H), 2.70-2.90 (m, 5H), 1.30 (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-6bda4c9177e247f39f34f330999d3500
Source dataset
uspto-grants-2008_11
Patent number
US07456292B2

Reaction notes

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