Morpholine → HCID 89781987, compound

HRID 1055981Notes

Reaction equation

HRID 1055981 reaction equation
C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:18]([OH:20])=O)[CH:14]=[CH:13]2.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[Br:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:18]([N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)=[O:20])[CH:14]=[CH:13]2

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 336959058-Bromoquinoline-2-carboxylic acid

Product 1

HCID 89781987HCID 89781987, compoundYield 97.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

At 0° C., oxalyl chloride (2.0 M solution in DCM, 2.73 mL, 5.47 mmol) was added to a suspension of 8-bromoquinoline-2-carboxylic acid (Princeton BioMolecular Research, Monmouth Junction, N.J.; 690 mg, 2.74 mmol) in 5 mL of DCM followed by 3 drops of DMF. The heterogeneous mixture was stirred at RT for 1 h, and it became homogeneous. The volatiles were removed in vacuo, and the residual brown solid was dissolved in 10 mL of DCM and cooled with an ice bath. Morpholine (0.29 mL, 3.28 mmol) and Et3N (0.46 mL, 3.28 mmol) were added. The reaction was stirred at RT for 1 h. The mixture was then diluted with 50 mL of DCM, washed sequentially with 5 mL of 0.5 N HCl, 5 mL of water, 5 mL of 0.5 N NaOH and 5 mL of brine. The DCM solution was dried over Na2SO4 and concentrated to give a brown oil. Re-crystallization from ether/hexanes gave (8-bromoquinolin-2-yl)(morpholino)methanone (855 mg, 97% yield) as a tan crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.60 (1H, d, J=8.6 Hz), 8.22 (1H, m), 8.10 (1H, d, J=8.0 Hz), 7.86 (1H, d, J=8.4 Hz), 7.61 (1H, t, J=7.8 Hz), 3.79 (4H, br.), 3.69 (4H, br). m/z (ESI, +ve) 321/323 (M+H)+.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe residual brown solid was dissolved in 10 mL of DCM
  3. temperaturecooled with an ice bath
  4. stirringThe reaction was stirred at RT for 1 h
  5. washwashed sequentially with 5 mL of 0.5 N HCl, 5 mL of water, 5 mL of 0.5 N NaOH and 5 mL of brine
  6. dry with materialThe DCM solution was dried over Na2SO4
  7. concentrationconcentrated
  8. customto give a brown oil

Sources & evidence

ORD record
ord-7d2a0e352afe483f910313d5fbf552ea
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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