Morpholine → Spiro[2H-1,3-benzoxazine-2,4'-piperidin]-4(3H)-one

HRID 1639527Notes

Reaction equation

HRID 1639527 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.C(N[C:12]1[CH:13]=[CH:14][C:15](O)=[C:16]([CH:20]=1)[C:17]([NH2:19])=[O:18])(=O)C.N1CCOCC1>CO.C(OCC)(=O)C>[NH:1]1[CH2:6][CH2:5][C:4]2([NH:19][C:17](=[O:18])[C:16]3[CH:20]=[CH:12][CH:13]=[CH:14][C:15]=3[O:7]2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 337214-PiperidoneHCID 10330248Benzamide, 5-(acetylamino)-2-hydroxy-

Product 1

HCID 379969Spiro[2H-1,3-benzoxazine-2,4'-piperidin]-4(3H)-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 24 mg (0.077 mmol) of N-[4,8-dimethoxyquinoline-2-yl)carbonyl]-4-piperidone, 15 mg (0.077 mmol) of 5-acetamido-2-hydroxybenzamide, and 0.020 mL of morpholine in 3 mL of methanol is refluxed for 48 hr. The reaction mixture is diluted with ethyl acetate, and washed with water, brine, and dried over Na2SO4. After solvent removal by rotoevaporation, the crude product is purified by preparative TLC to give 11 mg (0.022 mmol, 30% yield) of 6-acetamido-1′-[4,8-dimethoxyquinoline-2-yl)carbonyl]spiro[2H-1,3-benzoxazin-2,4′-piperidin]-4-(3H)-one (Compound 9): 1H NMR (DMSO-d6): δ 2.02 (s, 3H), 3.95 (s, 3H), 4.06 (s, 3H), 7.03 (d, 1H), 8.19 (s, 1H), 7.24 (d of d, 1H), 7.52 (d of d, 1H), 7.67 (m, 2H), 8.02 (d, 1H), 8.82, (s, 1H) and 9.98 ppm (s, 1H). MS m/z: 491.1 (M+H)+, 513.2 (M+Na)+.

Workup

  1. temperatureis refluxed for 48 hr
  2. washwashed with water, brine
  3. dry with materialdried over Na2SO4
  4. customAfter solvent removal by rotoevaporation
  5. customthe crude product is purified by preparative TLC

Sources & evidence

ORD record
ord-764a21ddb1184ccebf879e23a3e47f8b
Source dataset
uspto-grants-2012_02
Patent number
US08110570B2

Reaction notes

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