4-(2-Propyn-1-yl)morpholine → 5-(Morpholin-4-yl)pent-3-yn-2-one

HRID 42487

Reaction equation

HRID 42487 reaction equation
CC#N.C(=O)=O.[CH2:7]([N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[C:8]#[CH:9].C([Mg]Cl)(C)C.CON(C)[C:24](=[O:26])[CH3:25]>C1COCC1>[N:10]1([CH2:7][C:8]#[C:9][C:24](=[O:26])[CH3:25])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1

Participants

6

Reactant 4

HCID 4129414-(2-Propyn-1-yl)morpholineHCID 537505N-Methoxy-N-methylacetamideHCID 86587134Acetonitrile dry iceHCID 178418918HCID 178418918, compound

Product 1

HCID 674677495-(Morpholin-4-yl)pent-3-yn-2-oneYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a cooled (−40° C., CH3CN/CO2) solution of 4-(2-propyn-1-yl)morpholine (2.2 g, 17.58 mmol) in THF (5 mL) was added dropwise via. syringe under N2 a solution of 2 M isopropylmagnesium chloride in THF (10 mL, 20.00 mmol). The reaction was stirred for 1 hr then a solution of N-methoxy-N-methylacetamide (2.2 mL, 20.69 mmol) in THF (5 mL) was added in one portion. The reaction was stirred for 2 hr (allowed to slowly warm to RT), quenched with aq. NH4Cl, extracted with EtOAc, washed with brine, dried (Na2SO4), filtered and evaoprated to dryness under vacuum. The remaining was purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 80% EtOAc in hexanes). The pure fractions were combined and evaporated to dryness to give the product 5-(4-morpholinyl)-3-pentyn-2-one (2.09 g, 12.50 mmol, 71.1% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 3.62-3.57 (m, 4H), 3.56 (s, 2H), 2.49-2.43 (m, 4H), 2.34 (s, 3H). MS (ES)+m/e 168.0 [M+H]+.

Workup

  1. additionwas added dropwise via
  2. stirringThe reaction was stirred for 2 hr (
  3. customquenched with aq. NH4Cl
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customThe remaining was purified by silica gel chromatography (Analogix
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-a3f026059e8543d98e2d5f72a88f12b1
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Linked notes

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