Morpholine → 4-(4-Azidobenzoyl)morpholine

HRID 1520004Notes

Reaction equation

HRID 1520004 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[N:23]([C:26]1[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[CH:28][CH:27]=1)=[N+:24]=[N-:25].CCN(C(C)C)C(C)C.[NH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1>CN(C=O)C.CCOC(C)=O>[N:23]([C:26]1[CH:27]=[CH:28][C:29]([C:30]([N:44]2[CH2:49][CH2:48][O:47][CH2:46][CH2:45]2)=[O:32])=[CH:33][CH:34]=1)=[N+:24]=[N-:25]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 30341844-Azidobenzoic acid

Product 1

HCID 866990054-(4-Azidobenzoyl)morpholineYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

TBTU (1.28 g; 3.98 mmol; 1.3 eq.) was added to a cooled (0° C.) solution of 4-azidobenzoic acid (500 mg; 3.06 mmol; 1.0 eq.) and DIEA (1.2 mL; 7.05 mmol; 2.3 eq.) in DMF (10 mL). After 15 min, morpholine (324 μl; 3.68 mmol; 1.2 eq.) was added and the reaction mixture was stirred at RT for 3 hours. The reaction mixture was diluted with EtOAc and washed twice with an aqueous saturated solution of NaHCO3 then with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated to afford the title compound as a beige solid (710 mg, 100%). 1H NMR (300 MHz, DMSO-d6) δ 7.46 (d, J=8.6 Hz, 2H), 7.18 (d, J=8.6 Hz, 2H), 3.59-3.47 (m, 8H). HPLC (Condition A): Rt 2.21 min (purity 98.2%).

Workup

  1. washwashed twice with an aqueous saturated solution of NaHCO3
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-39905eaa79bc4a21828f4366139ab3ec
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

Loading…