Triethylamine → 3-Methoxy-cyclohexylamine

Temperature

0 °C

A mixture of 3-methoxycyclohexanecarboxylic acid, mixture of cis and trans 97% (1.50 g, 9.5 mmol), diphenylphosphoryl azide (2.043 mL, 9.5 mmol), and triethylamine (1.582 mL, 11.4 mmol) in anhydrous toluene (65 mL) was heated at reflux for 3 hrs. The mixture was cooled to 0° C., sodium trimethylsilanolate (18.964 mL of a 1 M solution in tetrahydrofuran, 19.0 mmol) was added, and the mixture stirred for 30 mins at room temperature. The reaction was quenched with 5% aqueous citric acid (100 mL), stirred, concentrated to approximately half volume under reduced pressure, washed with diethyl ether (2×), adjusted to basic pH with sodium hydroxide, and extracted with methylene chloride (3×). The combined organic layers were washed with saturated aqueous sodium chloride, dried (anhydrous sodium sulfate), filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography (5-12% methanol/methylene chloride) to give partially purified material. The residue was dissolved in methylene chloride and extracted with 1 N aqueous hydrochloric acid (3×). The combined aqueous layers were adjusted to basic pH with 15% aqueous sodium hydroxide and extracted with methylene chloride (3×). The combined organic fractions were dried (anhydrous sodium sulfate), filtered, concentrated, suspended in hexanes/methylene chloride, and filtered. Concentration of the organics gave a yellow liquid (0.272 g). 1H NMR (300 MHz, CDCl3) (mixture of diastereomers) δ 3.52 (m, 1H), 3.28 (s, 3H), 2.99 (m, 1H), 1.95-1.00 (m, 10H).

1. temperaturewas heated
2. temperatureat reflux for 3 hrs
3. customThe reaction was quenched with 5% aqueous citric acid (100 mL)
4. stirringstirred
5. concentrationconcentrated to approximately half volume under reduced pressure
6. washwashed with diethyl ether (2×)
7. extractionextracted with methylene chloride (3×)
8. washThe combined organic layers were washed with saturated aqueous sodium chloride
9. dry with materialdried (anhydrous sodium sulfate)
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe crude material was purified by silica gel chromatography (5-12% methanol/methylene chloride)
13. customto give partially purified material
14. extractionextracted with 1 N aqueous hydrochloric acid (3×)
15. extractionextracted with methylene chloride (3×)
16. dry with materialThe combined organic fractions were dried (anhydrous sodium sulfate)
17. filtrationfiltered
18. concentrationconcentrated
19. filtrationfiltered

ORD record

ord-bba30dadb5d44cd1a6563a177feb4d27

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09265772B2