Diisopropylamine → 4-Tert-butyl 1-methyl 2-(benzyloxy)-3-hydroxyfumarate

Temperature

-78 °C

Lithium diisopropylamide was generated by addition of n-butyl lithium (17 mL, 1.9M in hexane, 33.33 mmol), di-isopropyl amine (4.66 mL, 33.33 mmol) in tetrahydrofuran (15 mL) at 0° C. and stirred for 10 min. In a separate flask, a mixture of benzyloxy-acetic acid methyl ester (3) (4 g, 22.22 mmol) and oxalic acid tert-butyl ester methyl ester (2) (5.33 g, 33.33 mmol) in tetrahydrofuran (50 mL) was cooled to −78° C. and then lithium diisopropylamide was added at −78° C. The mixture was stirred at −78° C. for 1 h. After 1 h, the reaction mixture was allowed to warm to room temperature and stirred at room temperature for another 1 h. After completion of the reaction, the reaction was quenched with 1N HCl, and extracted with ethyl acetate. The separated organic part was dried over sodium sulfate and concentrated under reduced pressure, passed over a normal silica column using 25% ethyl acetate in hexane to get (E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester 1-methyl ester (4) (2.4 g, 35%) as ketoenol tautomers and ketone hydrate as a thick light yellow coloured oil. These were immediately used for next step.

1. stirringThe mixture was stirred at −78° C. for 1 h
2. waitAfter 1 h
3. temperatureto warm to room temperature
4. stirringstirred at room temperature for another 1 h
5. customAfter completion of the reaction
6. customthe reaction was quenched with 1N HCl
7. extractionextracted with ethyl acetate
8. dry with materialThe separated organic part was dried over sodium sulfate
9. concentrationconcentrated under reduced pressure

ORD record

ord-a0cae11fe7e24feebbe4eaba8adb6302

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045486B2