Methyl iodide → HCID 13082495, compound

To a suspension of 60% NaH in an oil dispersion (20 g, 500 mmol) in THF (600 mL) at 0° C. is added a solution of α-tetralone (24.8 g, 166.5 mmol) in THF (40 mL) via cannula, followed by iodomethane (119 g, 833 mmol). The reaction is permitted to warm to room temperature and after one hour is quenched with 1 M aqueous sodium bisulfate. The reaction mixture is partitioned between water and ethyl acetate and the organic layer is washed with brine, dried over magnesium sulfate, filtered and concentrated. The resulting residue is then dissolved in methanol (600 mL) and dichloromethane (100 mL). Sodium borohydride (37.8 g, 262 mmol) is then added in five portions over 20 minutes. After one hour the reaction is diluted with water, and the organic solvents are then evaporated in vacuo. The resulting mixture is extracted with ethyl acetate, and the organic extract is dried with magnesium sulfate, filtered and concentrated. The resulting residue is then dissolved in dichloromethane (300 mL). To the resulting solution is added triethylamine (50 g, 490 mmol) and 4-dimethylaminopyridine (4 g, 33 mmol). The reaction is cooled to 0° C. and charged with acetic anhydride (42 g, 408 mmol). The reaction is permitted to stir for 10 minutes, then is diluted with ethyl acetate, and washed with 1 M aqueous NaHSO41 followed by saturated aqueous NaHCO3. The organic phase is dried with magnesium sulfate, filtered, and concentrated. The resulting oil is then purified by distillation (110° C. at 0.2 torr) to furnish acetic acid 2,2-dimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl ester; 1H NMR (400 MHz, CDCl3) δ ppm 0.95 (s, 3 H), 1.01 (s, 3 H), 1.50-1.63 (m, 1 H), 1.84-1.99 (m, 1 H), 2.10 (s, 3 H), 2.76-2.94 (m, 2 H), 5.74 (s, 1 H), 7.08-7.31 (m, 4 H).

1. customis quenched with 1 M aqueous sodium bisulfate
2. customThe reaction mixture is partitioned between water and ethyl acetate
3. washthe organic layer is washed with brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe resulting residue is then dissolved in methanol (600 mL)
8. customthe organic solvents are then evaporated in vacuo
9. extractionThe resulting mixture is extracted with ethyl acetate
10. extractionthe organic extract
11. dry with materialis dried with magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. dissolutionThe resulting residue is then dissolved in dichloromethane (300 mL)
15. temperatureThe reaction is cooled to 0° C.
16. washwashed with 1 M aqueous NaHSO41
17. dry with materialThe organic phase is dried with magnesium sulfate
18. filtrationfiltered
19. concentrationconcentrated
20. distillationThe resulting oil is then purified by distillation (110° C. at 0.2 torr)

ORD record

ord-900bf20be1d34f26a9235b1081afcda1

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436035B2