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

HRID 593866Notes

Reaction equation

HRID 593866 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 2M 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 evaporated to dryness under vacuum. The remaining was purified by silica gel chromatography (Analogix, SF25-60g, 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. customevaporated to dryness under vacuum
  9. customThe remaining was purified by silica gel chromatography (Analogix, SF25-60g, 0 to 80% EtOAc in hexanes)
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-66c53751766346a59af00ac47b3053c7
Source dataset
uspto-grants-2016_01
Patent number
US09242962B2

Reaction notes

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