Reaction #90664

Reaction equation

CH3CN CO2

4-(2-propyn-1-yl)morpholine

N-methoxy-N-methylacetamide

isopropylmagnesium chloride

→

5-(4-morpholinyl)-3-pentyn-2-one

Yield 71.1%

Solvents

THF

THF

THF

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise via
2. 2
   workup.STIRRINGThe reaction was stirred for 2 hr (
3. 3
   Otherquenched with aq. NH4Cl
4. 4
   Extractionextracted with EtOAc
5. 5
   Washwashed with brine
6. 6
   Dryingdried (Na2SO4)
7. 7
   Filtrationfiltered
8. 8
   Otherevaporated to dryness under vacuum
9. 9
   OtherThe remaining was purified by silica gel chromatography (Analogix
10. 10
    Otherevaporated to dryness

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 evaporated 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]+.

Source