تفاعل #474692

معادلة التفاعل

(S)-tert-butyl 2-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-1-carboxylate

Lithium hydroxide hydrate

THF water

hydrogen peroxide

→

(S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid

المردود 72.0%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   workup.DISSOLUTIONuntil dissolved
2. 2
   workup.STIRRINGstirred for 10 minutes
3. 3
   workup.STIRRINGThe reaction was stirred for 30 minutes at 0° C
4. 4
   درجة الحرارةto warm to ambient temperature
5. 5
   workup.STIRRINGstirred overnight
6. 6
   أخرىThe reaction was quenched by addition of 1.5 M Na2SO3 (1 mL)
7. 7
   workup.STIRRINGstirred for 15 minutes
8. 8
   workup.ADDITIONThe reaction mixture was diluted with Et2O
9. 9
   أخرىseparated
10. 10
    غسيلThe aqueous portion was washed (2×) with Et2O
11. 11
    استخلاصThe aqueous portion was extracted (3×) with ethyl acetate
12. 12
    غسيلThe combined organic layers were washed with water (2×), saturated NaCl
13. 13
    تجفيفdried over Na2SO4
14. 14
    تركيزconcentrated in vacuo to a thick oil which

الإجراء التجريبي

Lithium hydroxide hydrate (0.0471 g, 1.12 mmol) was added to a solution of THF/water (3:1, 19 mL) and stirred until dissolved. The mixture was cooled to 0° C. and treated with 30% hydrogen peroxide (0.231 mL, 2.24 mmol) and stirred for 10 minutes. A solution of (S)-tert-butyl 2-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-1-carboxylate (0.280 g, 0.561 mmol) in THF (2 mL) was added. The reaction was stirred for 30 minutes at 0° C. TLC did not show much progress, therefore the reaction was allowed to warm to ambient temperature and stirred overnight. The reaction was quenched by addition of 1.5 M Na2SO3 (1 mL) and stirred for 15 minutes. The reaction mixture was diluted with Et2O and separated. The aqueous portion was washed (2×) with Et2O then adjusted to a pH of 1 with 3N HCl. The aqueous portion was extracted (3×) with ethyl acetate. The combined organic layers were washed with water (2×), saturated NaCl, dried over Na2SO4 and concentrated in vacuo to a thick oil which slowly solidified to give (S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid as a foam (0.55 g, 72%). 1H NMR (CDCl3, 400 MHz) δ 7.30 (d, 2H), 7.21 (d, 2H), 4.53-4.40 (m, 1H), 4.37-4.27 (m, 1H), 3.34-3.22 (m, 1H), 2.98-2.90 (m, 1H), 2.02-1.90 (m, 1H), 1.83-1.74 (m, 1H), 1.64-1.53 (m, 2H), 1.50 (s, 9H).

المصدر