Reaktion #47315

Reaktionsgleichung

p-toluene sulfonic acid

ethyl iodide

(S)-4-((R)-2-hydroxy-propyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester

sodium hydride

→

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

Lösungsmittel

tetrahydrofuran

methanol

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionextracted with diethyl ether and saturated sodium chloride solution
2. 2
   WaschenThe organic layer was washed with saturated sodium chloride solution
3. 3
   Trocknendried over sodium sulfate
4. 4
   SonstigeAfter the evaporation of solvents
5. 5
   Sonstigean oily material was obtained (660 mg)
6. 6
   workup.STIRRINGThe mixture was stirred at room temperature overnight
7. 7
   SonstigeSolvents were evaporated
8. 8
   Extraktionthe residue was extracted with ethyl acetate and sodium bicarbonate solution
9. 9
   SonstigeAfter the evaporation of solvents
10. 10
    workup.DISSOLUTIONthe resulting oily compound (532 mg) was dissolved in a mixture of acetonitrile (11 mL) and phosphate buffer (8 mL, pH=7)
11. 11
    workup.ADDITIONThen 1-oxyl-2,2,6,6-tetramethylpiperidine (24 mg) and sodium chlorite (495 mg) in water (2.5 mL) were added
12. 12
    TemperaturThe solution was warmed to 35° C.
13. 13
    workup.ADDITIONcatalytic amount of diluted bleach (1 mL of 5.25% sodium hypochlorite solution diluted to 20 mL in water, 1 mL of the diluted solution was used)
14. 14
    workup.ADDITIONwas added in 5 portions
15. 15
    workup.STIRRINGThe mixture was stirred for 2 h
16. 16
    workup.ADDITIONThen second portion of sodium chlorite (495 mg) in water (2.5 mL) was added
17. 17
    workup.STIRRINGThe mixture was stirred at room temperature overnight
18. 18
    TemperaturThe mixture was cooled to 0° C.
19. 19
    workup.ADDITIONSodium sulfite solution (2.7 g) in water (30 mL) was added
20. 20
    workup.STIRRINGthe mixture was stirred for 20 min
21. 21
    ExtraktionThe resulting solution was extracted with methyl t-butyl ether
22. 22
    ExtraktionThe mixture was extracted with methyl t-butyl ether three times
23. 23
    Trocknendried over sodium sulfate
24. 24
    SonstigeSolvents were evaporated

Vorschrift

To a cooled solution of (S)-4-((R)-2-hydroxy-propyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester (730 mg, 2.81 mmol) in dry tetrahydrofuran (15 mL) was added sodium hydride at 0° C. (60% in mineral oil, 248 mg). The suspension was warmed to room temperature and ethyl iodide (1.2 mL) was added. The mixture was stirred overnight 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 (660 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 (22 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 (532 mg) was dissolved in a mixture of acetonitrile (11 mL) and phosphate buffer (8 mL, pH=7). Then 1-oxyl-2,2,6,6-tetramethylpiperidine (24 mg) and sodium chlorite (495 mg) in water (2.5 mL) 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 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 (495 mg) in water (2.5 mL) 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 g) in water (30 mL) was added and the mixture was stirred for 20 min. The resulting solution was extracted with methyl t-butyl ether. The organic layer was discarded and the aqueous layer was acidified with 1N aqueous hydrochloric acid to pH value about 2.0. The mixture was extracted with methyl t-butyl ether three times and dried over sodium sulfate. Solvents were evaporated to afford (2S,4R)-2-t-butoxycarbonylamino-4-ethoxy-pentanoic acid (279 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 (t, 7.2 Hz, 3H), 1.22 (d, J=6.3 Hz, 3H), 1.46 (s, 9H), 1.88-2.16 (m, 2H), 3.26-3.43 (m, 1H), 3.55-3.72 (m, 2H), 4.27-4.39 (m, 1H), 5.59 (br. s., 1H), 10.51 (br. s., 1H).

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