Methyl iodide → HCID 178495629, compound

Temperature

0 °C

Sodium hydride (72 mg, 1.78 mmol, 60% by weight suspended in mineral oil) was washed three times with 10 mL portions of hexanes, and suspended in dry THF (12 mL). The suspension was cooled to 0° C. To this suspension, cis-(tert-butoxy)-N-[4-(hydroxymethyl)cyclohexyl]carboxamide (0.273 g, 1.20 mmol) and 15-crown-5 (0.250 mL, 1.25 mmol) were added. The reaction mixture was then stirred at 0° C. for about 30 min. Methyl iodide was then added dropwise (75 μL, 1.20 mmol). Since the reaction was not complete after overnight stirring at room temperature, the mixture was cooled to 0° C. and reacted with 100 mg of sodium hydride and 0.250 mL of 15-crown-5. After about 2 hours at room temperature, the reaction was complete. The reaction was quenched by the slow addition of water and the crude product was extracted with ethyl acetate. Purification was effected by column chromatography on silica gel using 20% ethyl acetate in hexanes as the eluent. ES-MS (m/z) 244. cis-(Tert-butoxy)-N-[4-(methoxymethyl)cyclohexyl]carboxamide was dissolved in ethanol (5 mL) and the solution was treated with 1 mL of acetyl chloride at room temperature. The reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure and the resulting solid was used without further purification. (79% yield) ES-MS (m/z) 144.

1. waitSince the reaction was not complete after overnight
2. stirringstirring at room temperature
3. temperaturethe mixture was cooled to 0° C.
4. waitAfter about 2 hours at room temperature
5. customThe reaction was quenched by the slow addition of water
6. extractionthe crude product was extracted with ethyl acetate
7. customPurification
8. dissolutioncis-(Tert-butoxy)-N-[4-(methoxymethyl)cyclohexyl]carboxamide was dissolved in ethanol (5 mL)
9. additionthe solution was treated with 1 mL of acetyl chloride at room temperature
10. stirringThe reaction mixture was stirred at room temperature overnight
11. customThe solvent was removed under reduced pressure
12. customthe resulting solid was used without further purification

ORD record

ord-04a0afa1b08c4da9981c0b4b38ced5b4

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101588B2