Hexamethylphosphoramide → Ethyl 2-hydroxy-6,6-dimethylcyclohex-1-enecarboxylate

Temperature

-5 °C

Into a 500 mL flame dried round-bottomed flask was added copper(I) iodide (18 g) in ether (200 mL) to give a suspension. After cooling to −5° C., methyllithium (120 mL, 1.6M in ether) was added dropwise. After stirring at −5° C. for 1 hour, 3-methylcyclohex-2-enone (5.15 mL) in 15 ml ether was added dropwise, and the mixture was stirred at −5° C. for 1 hour. After cooling to −78° C., hexamethylphosphoramide (60 mL) was added dropwise. Ethyl carbonocyanidate (23.74 mL) was added. After stirring at −78° C. for 20 minutes, the mixture was warmed up to room temperature, and stirred for 1 hour. The mixture was poured into cold water, and the layers were separated. The aqueous layer was extracted with ether (3×20 mL). The combined organic layers were washed with saturated aqueous NH4Cl (3×20 mL), dried over Na2SO4, filtered, and dried under vacuum. The crude product was added to a silica gel column and purified by eluting with 0-10% ethyl acetate in hexane.

1. temperatureInto a 500 mL flame dried round-bottomed flask
2. customto give a suspension
3. stirringthe mixture was stirred at −5° C. for 1 hour
4. temperatureAfter cooling to −78° C.
5. stirringAfter stirring at −78° C. for 20 minutes
6. temperaturethe mixture was warmed up to room temperature
7. stirringstirred for 1 hour
8. customthe layers were separated
9. extractionThe aqueous layer was extracted with ether (3×20 mL)
10. washThe combined organic layers were washed with saturated aqueous NH4Cl (3×20 mL)
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. customdried under vacuum
14. additionThe crude product was added to a silica gel column
15. custompurified
16. washby eluting with 0-10% ethyl acetate in hexane

ORD record

ord-fd71c6139f574343984e3b35000a0dab

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174982B2