Nitrogen → HCID 86657019, compound

In a flame-baked, two neck 100 mL round bottom flask, 20 mmol of L-alanine methyl ester hydrochloride (2.8 g), 40 mmol of K2CO3 (5.53 g), and 20 mmol of tetrabutylammonium iodide (TBAI, 7.39 g) were charged under a stream of dry N2 gas. 35 mL of tetrahydrofuran (THF) was slowly added and the mixture was stirred for 15 min at room temperature. 2.6 mL of 6-iodo-hex-1-yne was added dropwise while the mixture was stirred. The reaction mixture was refluxed at ˜70° C. for 15-18 h with TLC check. After consumption of the starting material, the mixture was cooled to room temperature, diluted by diethylether, and filtered. The filtrate was further diluted by diethylether and filtered again. The solvent was removed by rotavap and the crude product was purified by flash chromatography on silica gel (1:2=Hexane/EtOAc, 1% triethylamine) to give N-(5-hexynyl) L-alanine methyl ester (2.044 g, 11.2 mmol) as a yellow oil. Yield: 56%. Rf=0.27 (1:1=Hexane/EtOAc); ESI-MS [M+H]+=184.1 m/z; 1H NMR (300 MHz, CDCl3): δ 3.70 (s, 3H), 3.32 (q, J=7.0 Hz, 1H), 2.53 (m, 2H), 2.18 (m, 2H), 1.92 (t, J=2.6 Hz, 1H), 1.56 (m, 5H), 1.27 (d, J=7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 176.29, 84.21, 68.41, 56.61, 51.74, 47.41, 29.20, 26.01, 19.11, 18.23.

1. stirringwas stirred
2. temperatureThe reaction mixture was refluxed at ˜70° C. for 15-18 h with TLC check
3. customAfter consumption of the starting material
4. temperaturethe mixture was cooled to room temperature
5. additiondiluted by diethylether
6. filtrationfiltered
7. additionThe filtrate was further diluted by diethylether
8. filtrationfiltered again
9. customThe solvent was removed by rotavap
10. customthe crude product was purified by flash chromatography on silica gel (1:2=Hexane/EtOAc, 1% triethylamine)

ORD record

ord-3e73aec717fc41f795323919b9fb7421

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08309359B2