Methyl iodide → 4-METHYLTETRAHYDRO-2H-PYRAN-4-CARBOXYLIC ACID

Butyllithium (21.1 ml, 33.8 mmol, 1.6 M in hexanes) was added dropwise over 10 minutes to a stirred solution of diisopropylamine (4.7 ml, 33.8 mmol) in anhydrous tetrahydrofuran (40 ml) under an atmosphere of nitrogen at <10° C. Upon addition, tetrahydropyran-4-carboxylic acid (J. Am. Chem. Soc., 1993, 115, 8407) was added in anhydrous tetrahydrofuran (20 ml) under nitrogen at <5° C. The mixture was stirred at room temperature for one hour after which methyl iodide (2.4 ml, 38.4 mmol) was added dropwise at <5° C. The resultant solution was stirred at <50° C. for 30 minutes, allowed to warm to room temperature and stirred for a further 3.5 days. The solvent was removed by evaporation and the residue dissolved in dichloromethane (100 ml) and 2N hydrochloric acid (100 ml) added. The aqueous layer was extracted with dichloromethane (3×100 ml) and the combined organic layers were washed with water (100 ml), brine (100 ml), dried (MgSO4), filtered and evaporated to yield the title product (1.4 g) which was used in the next step without purification. Data for the title compound: 1H NMR (250 MHz, CDCl3) δ1.00 (3H, s), 1.47-1.58 (2H, m), 2.06-2.11 (2H, m), 3.49-3.60 (2H, m), 3.78-3.86 (2H, m).

1. additionwas added dropwise at <5° C
2. customThe solvent was removed by evaporation
3. dissolutionthe residue dissolved in dichloromethane (100 ml)
4. addition2N hydrochloric acid (100 ml) added
5. extractionThe aqueous layer was extracted with dichloromethane (3×100 ml)
6. washthe combined organic layers were washed with water (100 ml), brine (100 ml)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customevaporated

ORD record

ord-f356e9b1b8944eed8728429c5a658b65

Source dataset

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06579875B1