N-Formylmorpholine → HCID 76698013, compound

Temperature

-10 °C

4-Bromo-1-fluoro-2-(2-methoxyvinyl)benzene (limiting reagent) (step c) was dissolved in 2-methyltetrahydrofuran (5 volumes) and the solution cooled to −10° C. Iso-propylmagnesium chloride (0.37 molar equivalents of a 2M solution in THF) was added dropwise, keeping the temperature at −7° C. (+ or −2° C.), over about 30 minutes, followed by Butyllithium (0.74 molar equivalents of a 1.5M solution in hexane), controlling the temperature at −6° C. (+ or −2° C.), over about 1 hour. Stirred for 45 minutes then added to a solution of 4-formylmorpholine (2 molar equivalents) in 2-methyltetrahydrofuran (7 volumes) at −5° C. This addition took about 90 minutes. The reaction was then stirred for 1 hour, during which time the internal temperature rose to 5° C. The reaction mixture was poured into saturated aq. ammonium chloride solution (10 volumes) and extracted with t-BME (2×3 volumes). Combined extracts were washed with sat'd aq. ammonium chloride (until the pH of the washing was approx 6) (2×3 volumes), water (5 volumes), dried (Na2SO4), filtered and evaporated to give a mobile orange oil.

1. customat −7° C.
2. custom(+ or −2° C.)
3. customat −6° C.
4. custom(+ or −2° C.)
5. waitover about 1 hour
6. additionThis addition
7. waittook about 90 minutes
8. stirringThe reaction was then stirred for 1 hour, during which time the internal temperature
9. customrose to 5° C
10. extractionextracted with t-BME (2×3 volumes)
11. washCombined extracts were washed with sat'd aq. ammonium chloride (until the pH of the washing
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. customevaporated
15. customto give a mobile orange oil

ORD record

ord-6099e6d0dedc4a3d9e4a08436a7e3eeb

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148373B2