Diiodomethane → 1,3-Dimethyl 1-(iodomethyl)-1,3-cyclohexanedicarboxylate

Temperature

0 °C

A cooled (−67° C.) solution of dry diisopropylamine (3.65 mL, 26 mmol) in anhydrous THF (20 mL) under nitrogen was treated via syringe with 2.5N n-butyllithium/hexane (9.6 mL, 24 mmol), warmed to 0° C. for 5 min, then recooled (−67° C.). DMPU (12.1 mL, 100 mmol) was added dropwise via addition funnel so as to keep pot temp <−60° C., then a solution of dimethyl cyclohexane-1,3-dicarboxylate (4.00 g, 20 mmol) in anhydrous THF (10 mL) was likewise added dropwise. After 1 h at −67° C., diiodomethane (7.23 g, 27 mmol) in THF (10 mL) was added dropwise, then the mixture was warmed to room temperature over 1 h stirred 1 h, cooled on an ice bath, and quenched with saturated aqueous ammonium chloride (20 mL). The organic solvents were removed in vacuo and water (30 mL) was added, and the aqueous was extracted with hexane (100 mL, then 2×50 mL). The combined organic extracts were washed with water (75 mL), dried (MgSO4), and concentrated in vacuo, then dissolved in methylene chloride and passed through a pad of alumina in a fritted (30 mL) funnel. The concentrated filtrate was chromatographed on silica gel (˜200 cc, eluted with 1:1 hexane/methylene chloride) to afford 4.65 g (68%) of 1-iodomethyl-1,3-dicarbomethoxycyclohexane as a colorless oil.

1. custom(−67° C.)
2. customto keep pot temp <−60° C.
3. temperaturethe mixture was warmed to room temperature over 1 h
4. temperaturecooled on an ice bath
5. customquenched with saturated aqueous ammonium chloride (20 mL)
6. customThe organic solvents were removed in vacuo and water (30 mL)
7. additionwas added
8. extractionthe aqueous was extracted with hexane (100 mL
9. washThe combined organic extracts were washed with water (75 mL)
10. dry with materialdried (MgSO4)
11. concentrationconcentrated in vacuo
12. dissolutiondissolved in methylene chloride
13. custompassed through a pad of alumina in a fritted (30 mL) funnel
14. customThe concentrated filtrate was chromatographed on silica gel (˜200 cc, eluted with 1:1 hexane/methylene chloride)

ORD record

ord-04ec3399662a47498b617856c065f3c2

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07842707B2