Carbon Dioxide → [4,5-Dimethoxy-2-(1-methyl-2-phenyl-ethyl)-phenyl]-(2,4-dimethoxy-pyrimidin-5-yl)-methanol

Temperature

-78 °C

Freshly distilled 2,2,6,6-tetramethyl piperidine (0.85 mL, 5.0 mmol) was dissolved in 20 mL THF and cooled to 0° C. n-Butyllithium (2.0 mL, 2.5 M in hexanes) was added drop-wise over 5 minutes and the mixture was allowed to stir for 30 minutes and then cooled to −78° C. 2,4-Dimethoxypyrimidine (0.353 g, 2.52 mmol) was added drop-wise over 5 min. After 45 min the solution was transferred via a dry ice cooled cannula to a solution of 4,5-dimethoxy-2-(1-methyl-2-phenyl-ethyl)-benzaldehyde (0.717 g, 2.52 mmol) in 20 mL THF at −78° C. After stirring for 1 hour the solution was warmed to room temperature and quenched by the slow addition of 50 mL 10% NH4Cl. After 100 mL of H2O was added the mixture was extracted with ethyl acetate, washed with H2O and washed with brine. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give an orange oil. Purification via flash chromatography (3:2 hexane/ethyl acetate) afforded [4,5-dimethoxy-2-(1-methyl-2-phenyl-ethyl)-phenyl]-(2,4-dimethoxy-pyrimidin-5-yl)-methanol (0.551 g, 52%) as a clear oil.

1. additionwas added drop-wise over 5 minutes
2. stirringAfter stirring for 1 hour the solution
3. temperaturewas warmed to room temperature
4. customquenched by the slow addition of 50 mL 10% NH4Cl
5. additionAfter 100 mL of H2O was added the mixture
6. extractionwas extracted with ethyl acetate
7. washwashed with H2O
8. washwashed with brine
9. dry with materialThe combined organics were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto give an orange oil
13. customPurification via flash chromatography (3:2 hexane/ethyl acetate)

ORD record

ord-b1c9d276402648ec9a68efe9d4fc552b

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846705B2