Methanol → HCID 21911993, compound

Temperature

-50 °C

Under inert atmosphere, 0.91 g (4.6 mmol) of TOSMIC in solution in anhydrous DME (4 ml) is added to 0.96 g (8.6 mmol) of potassium tert-butylate in suspension in 4 ml of anhydrous DME at −35° C. The reaction mixture is cooled to −50° C. then 1 g (4.4 mmol) of 1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbaldehyde (Whitten J P, JOC 1986, 51 (10) 1891-1894) in solution in 4 ml of anhydrous DME is added dropwise, keeping the temperature below −45° C. The reaction mixture is stirred at this temperature for 30 min, then 11 ml of methanol is added, and the mixture is heated at 80° C. for 15 minutes. The solvents are concentrated under reduced pressure, and the residue is taken up in a water/acetic acid mixture (13 ml/0.5 ml), the aqueous phase is extracted with dichloromethane (3×100 ml), the organic phases are then washed with a saturated solution of NaHCO3, then dried over Na2SO4. After filtration, the filtrate is concentrated under reduced pressure and the residue is purified by filtration on basic alumina (eluent: A/B=DCM/AcEt 0 to 50% of B), 0.71 g of compound is thus obtained in the form of a yellowish orange oil. Yield=67%. MH+: 238 (Tr: 6.9 min, condition 1).

1. customthe temperature below −45° C
2. temperaturethe mixture is heated at 80° C. for 15 minutes
3. concentrationThe solvents are concentrated under reduced pressure
4. extractionthe aqueous phase is extracted with dichloromethane (3×100 ml)
5. washthe organic phases are then washed with a saturated solution of NaHCO3
6. dry with materialdried over Na2SO4
7. filtrationAfter filtration
8. concentrationthe filtrate is concentrated under reduced pressure
9. filtrationthe residue is purified by filtration on basic alumina (eluent

ORD record

ord-1a4561022d1f4cdd884dd2b4f465a37f

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623893B2