Water → HCID 118126837, compound

Temperature

0 °C

To a solution of (methoxymethyl)triphenylphosphonium chloride (1.7 g, 5.0 mmol) in THF (10 mL) was added sodium hydride (108 mg, 4.5 mmol, 60 wt %) in several portions at 0° C. The resulting mixture was stirred at 0° C. for 1 hour. Then ethyl rel-(1R,2S)-2-methyl-4-oxocyclohexanecarboxylate (500 mg, 2.7 mmol) in THF (5 mL) was added dropwise at 0° C. and the reaction mixture was stirred at room temperature overnight. Water was then added dropwise at 0° C. and the mixture was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to give ethyl rel-(1R,2S)-4-(methoxymethylidene)-2-methylcyclohexanecarboxylate, which was dissolved in THF and aqueous hydrochloric acid (6 M) was added dropwise at 0° C. The reaction mixture was stirred at room temperature for 2 hours and then diluted with water. The mixture was extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure to give ethyl rel-(1R,2S)-4-formyl-2-methylcyclohexanecarboxylate. MS ESI calc'd for C11H19O3 [M+H]+ 199. found 199. 1H NMR: (400 MHz, CDCl3) δ 9.67-9.57 (m, 1H), 4.22-4.05 (m, 2H), 2.65-1.52 (m, 9H), 1.25 (t, J=7.2 Hz, 3H), 1.03-0.88 (m, 3H).

1. stirringthe reaction mixture was stirred at room temperature overnight
2. extractionthe mixture was extracted with ethyl acetate
3. dry with materialThe combined organic layers were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether)

ORD record

ord-b3f72b57ab0c48f8a216e366f911bd6e

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09416111B2