Ammonium Chloride → 5-(Morpholin-4-yl)pent-3-yn-2-one

Temperature

-40 °C

4-Prop-2-ynyl-morpholine (22 g, 176 mmol) was dissolved under nitrogen in THF (40 mL) and cooled to −40° C. Then a 2 M solution of isopropyl magnesium chloride in THF (97 mL, 193 mmol) was added while keeping the temperature below −20° C. Stirring at −40° C. to −30° C. was continued for 30 min. In a separate flask, N-methoxy-N-methylacetamide (20 g, 193 mmol) was dissolved under nitrogen in THF (40 mL) and cooled to −10° C. in ice/MeOH. The Grignard solution prepared above was transferred to the Weinreb amide solution at −10° C. via teflon tubing under slightly positive nitrogen pressure in vessel 1. There was no exotherm. Stirring at −10° C. to 0° C. was continued for 2 h. Ther resulting white suspension was poured on a 1:1-mixture of ice and saturated NH4Cl solution (400 mL). Extraction: 2×AcOEt, 1× saturated NaCl solution. One obtained a yellow oil (26.1 g, 89%). Chromatography on silica gel in heptane/ethyl acetate 1:2 gave 19.4 g (66%) of a brown oil which was distilled in the Kugelrohr at 130° C./0.2 mbar. One obtained 15.8 g (53%) of a yellow oil.

1. customthe temperature below −20° C
2. customThe Grignard solution prepared
3. stirringStirring at −10° C. to 0° C.
4. waitwas continued for 2 h
5. additionTher resulting white suspension was poured on a 1
6. extractionExtraction

ORD record

ord-8ac44c3d41f34aef92311f2fcf30babb

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07351700B2