Dimethyl Sulfate → HCID 18003645, compound

Temperature

0 °C

The azide (171.8 g, 1.22 mol) and tetrabutylammonium hydrogensulfate (4.2 g, 12.4 mmol) are sequentially added to a solution of methylene chloride (700 ml) and a 50% w/w aqueous solution of sodium hydroxide (129 g in 129 ml of water). The resulting mixture is vigorously stirred for 30 minutes before being cooled to 0° C. Dimethyl sulfate (186 g, 140 ml, 1.48 mol) is added in a dropwise manner to the vigorously stirred solution over a period of one hour, during which time a solid mass forms. This is broken up by addition of a further portion of methylene chloride (150 ml). The reaction mixture is then allowed to warm to room temperature and stirred for 20 hours. TLC analysis indicates a small amount of alcohol still remaining, and thus the reaction is allowed to proceed for an additional 12 hours at 50° C. After cooling to room temperature, the reaction is quenched by addition of concentrated ammonium hydroxide solution (100 ml) and allowed to stir for 45 minutes. The mixture is poured into water (500 ml) and extracted with methylene chloride (2×500 ml). The organic extracts are washed with water (3×500 ml) until the washings are neutral. The extracts are dried over sodium sulfate and the volatiles removed in vacuo. The crude product is passed through a plug of silica eluting with hexanes:ethyl acetate (9:1) to yield 1-azido-2-methoxycyclohexane (110 g, 58%) as a colorless oil.

1. temperatureto warm to room temperature
2. stirringstirred for 20 hours
3. waitto proceed for an additional 12 hours at 50° C
4. temperatureAfter cooling to room temperature
5. customthe reaction is quenched by addition of concentrated ammonium hydroxide solution (100 ml)
6. stirringto stir for 45 minutes
7. additionThe mixture is poured into water (500 ml)
8. extractionextracted with methylene chloride (2×500 ml)
9. washThe organic extracts are washed with water (3×500 ml) until the washings
10. dry with materialThe extracts are dried over sodium sulfate
11. customthe volatiles removed in vacuo

ORD record

ord-73ca34851e564db7bba212139de48e3c

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06642390B2