Hydrochloric Acid → 3-(1,3-Dihydroxy-3-m-tolyl-propyl)-4-methoxy-benzoic acid methyl ester

Temperature

-78 °C

3-Acetyl-4-methoxy-benzoic acid methyl ester (150 mg, 0.720 mmol) was dissolved in THF (3 ml), cooled to −78° C., and a freshly prepared solution of lithium diisopropylamide (obtained by addition of n-butyllithium in n-hexane (0.317 ml, 2.5 M solution) to diisopropylamine (80.1 mg, 0.792 mmol) in THF (3 ml) at 0° C. and stirring for 10 min) was slowly added with stirring. After 10 min, 3-methylbenzaldehyde (86.5 mg, 0.720 mmol) was added at −78° C. After 30 min at −78° C., 2 N hydrochloric acid and EA were added, the cooling bath was removed, the mixture was brought to room temperature. The phases were separated, the aqueous phase was extracted three times with EA, the combined organic extracts were dried over sodium chloride, decanted and evaporated to dryness. The residue was dissolved in methanol (5 ml), sodium borohydride (28.7 mg, 0.761 mmol) was added, and the mixture was stirred at room temperature for 30 min. The mixture was evaporated to dryness and the residue was purified by silica gel chromatography (HEP/EA gradient) to give 140 mg of the title compound as a mixture of diastereomers.

1. waitAfter 30 min at −78° C.
2. customthe cooling bath was removed
3. customwas brought to room temperature
4. customThe phases were separated
5. extractionthe aqueous phase was extracted three times with EA
6. dry with materialthe combined organic extracts were dried over sodium chloride
7. customdecanted
8. customevaporated to dryness
9. dissolutionThe residue was dissolved in methanol (5 ml)
10. stirringthe mixture was stirred at room temperature for 30 min
11. customThe mixture was evaporated to dryness
12. customthe residue was purified by silica gel chromatography (HEP/EA gradient)

ORD record

ord-5ef8c948783c456db4f392839590f66a

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802720B2