Citric Acid → Methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate

The compound (9.0 g) obtained in Referential Example 161 and triethylamine (9.7 ml) were dissolved in tetrahydrofuran (180 ml), and the solution was cooled to −10° C., to which isobutyl chloroformate (9.1 ml) was added dropwise, and the resultant mixture was stirred for 1 hour. On the other hand, sodium borohydride (7.1 g) was dissolved in tetrahydrofuran (100 ml)-water (25 ml) and cooled with ice. While removing insoluble matter by filtration, the solution prepared previously was added dropwise, and the resultant mixture was stirred at the same temperature for 1 hour. The reaction mixture was poured into a cooled 10% aqueous solution of citric acid to conduct extraction with ethyl acetate. After the extract was washed with saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:9-2:1) to obtain the title compound (4.25 g).

1. additionwas added dropwise
2. temperaturecooled with ice
3. customWhile removing insoluble matter
4. filtrationby filtration
5. customthe solution prepared previously
6. additionwas added dropwise
7. extractionextraction with ethyl acetate
8. washAfter the extract was washed with saturated aqueous solution of sodium chloride
9. dry with materialdried over anhydrous sodium sulfate
10. distillationthe solvent was distilled off under reduced pressure
11. customThe resultant residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:9-2:1)

ORD record

ord-edcba37e7f814b009472de32b6b384dc

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07365205B2