Iodoethane → (2S,4S)-2-t-butoxycarbonylamino-4-ethoxy-pentanoic acid

To a cooled solution of (S)-4-((S)-2-hydroxy-propyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester (prepared as in Example 94, 860 mg, 3.32 mmol) in dry tetrahydrofuran (15 mL) was added sodium hydride at 0° C. (60% in mineral oil, 292 mg). The suspension was warmed to room temperature and ethyl iodide (1.2 mL) was added. The mixture was stirred at room temperature for 20 h and extracted with diethyl ether and saturated sodium chloride solution. The organic layer was washed with saturated sodium chloride solution and dried over sodium sulfate. After the evaporation of solvents, an oily material was obtained (966 mg). This oily material was dissolved in a mixture of tetrahydrofuran (1 mL) and methanol (10 mL). To this solution was added p-toluene sulfonic acid monohydrate (32 mg). The mixture was stirred at room temperature overnight. Solvents were evaporated and the residue was extracted with ethyl acetate and sodium bicarbonate solution. After the evaporation of solvents, the resulting oily compound (800 mg) was dissolved in a mixture of acetonitrile (17 mL) and phosphate buffer (12 mL, pH=7). Then 1-oxyl-2,2,6,6-tetramethylpiperidine (41 mg) and sodium chlorite solution (731 mg in 4.0 mL of water) were added. The solution was warmed to 35° C. and catalytic amount of diluted bleach (1 mL of 5.25% sodium hypochlorite solution diluted to 20 mL in water, 1.6 mL of the diluted solution was used) was added in 5 portions. The mixture was stirred for 2 h. Then second portion of sodium chlorite (750 mg in 4.0 mL of water) was added. The mixture was stirred at room temperature overnight. The mixture was cooled to 0° C. and adjusted to pH=9 with dilute sodium hydroxide solution. Sodium sulfite solution (2.7 vg in 30 mL of water) was added and the mixture was stirred for 20 min. The resulting solution was extracted with methyl t-butyl ether. Organic layer was discarded and the aqueous layer was acidified with 1N aqueous hydrochloric acid to a pH value of about 2.0. The mixture was extracted with methyl t-butyl ether three times and dried over sodium sulfate. The solvents were evaporated to afford (2S,4S)-2-t-butoxycarbonylamino-4-ethoxy-pentanoic acid (401 mg) as a thick oil: LR-ES-MS m/z calculated for C12H23NO5 [M] 261, observed 260 [M−H]; 1H NMR (300 MHz, CDCl3) δ ppm 1.18-1.29 (m, 6H), 1.446 (s, 9H), 1.88-2.00 (m, 2H), 3.36-3.51 (m, 1H), 3.66-3.89 (m, 2H), 4.24-4.37 (m, 1H), 5.89 (d, J=4.5 Hz, 1H), 10.23 (br. s., 1H).

1. extractionextracted with diethyl ether and saturated sodium chloride solution
2. washThe organic layer was washed with saturated sodium chloride solution
3. dry with materialdried over sodium sulfate
4. customAfter the evaporation of solvents
5. customan oily material was obtained (966 mg)
6. stirringThe mixture was stirred at room temperature overnight
7. customSolvents were evaporated
8. extractionthe residue was extracted with ethyl acetate and sodium bicarbonate solution
9. customAfter the evaporation of solvents
10. dissolutionthe resulting oily compound (800 mg) was dissolved in a mixture of acetonitrile (17 mL) and phosphate buffer (12 mL, pH=7)
11. additionThen 1-oxyl-2,2,6,6-tetramethylpiperidine (41 mg) and sodium chlorite solution (731 mg in 4.0 mL of water) were added
12. temperatureThe solution was warmed to 35° C.
13. additioncatalytic amount of diluted bleach (1 mL of 5.25% sodium hypochlorite solution diluted to 20 mL in water, 1.6 mL of the diluted solution was used)
14. additionwas added in 5 portions
15. stirringThe mixture was stirred for 2 h
16. additionThen second portion of sodium chlorite (750 mg in 4.0 mL of water) was added
17. stirringThe mixture was stirred at room temperature overnight
18. temperatureThe mixture was cooled to 0° C.
19. additionSodium sulfite solution (2.7 vg in 30 mL of water) was added
20. stirringthe mixture was stirred for 20 min
21. extractionThe resulting solution was extracted with methyl t-butyl ether
22. extractionThe mixture was extracted with methyl t-butyl ether three times
23. dry with materialdried over sodium sulfate
24. customThe solvents were evaporated

ORDレコード

ord-5f09a878697647bb91b1e29999395576

出典データセット

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07741327B2