Triethylamine → (R)-4-benzyl-3-(2-(5-chlorothiophen-2-yl)acetyl)oxazolidin-2-one

HRID 559470

반응식

HRID 559470 반응식
C(N(CC)CC)C.[Cl:8][C:9]1[S:13][C:12]([CH2:14][C:15]([OH:17])=O)=[CH:11][CH:10]=1.CC(C)(C)C(Cl)=O.[CH2:25]([C@@H:32]1[CH2:36][O:35][C:34](=[O:37])[NH:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([Li])CCC>CCOCC.C1COCC1.CCCCCC>[CH2:25]([C@@H:32]1[CH2:36][O:35][C:34](=[O:37])[N:33]1[C:15](=[O:17])[CH2:14][C:12]1[S:13][C:9]([Cl:8])=[CH:10][CH:11]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

참가 물질

9

반응물 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinoneHCID 44267162-(5-chlorothiophen-2-yl)acetic AcidHCID 178418339Butyllithium

생성물 1

HCID 66618123(R)-4-benzyl-3-(2-(5-chlorothiophen-2-yl)acetyl)oxazolidin-2-one수율 56.2%

시약·촉매·용매 3

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매HCID 8058Hexane용매

반응 조건

온도
0 °C

실험 절차

Triethylamine (7.32 mL, 52.5 mmol) was added to a solution of 5-chlorothiophene-2-acetic acid (8.83 g, 50.0 mmol) in ether (200 mL) at −78° C., followed by 2,2-dimethylpropanoyl chloride (6.46 mL, 52.5 mmol). The resulting mixture was stirred at 0° C. for 2 hours, and then re-cooled to −78° C. Meanwhile, a solution of (R)-4-benzyl-2-oxazolidinone (9.30 g, 52.5 mmol) in THF (100 mL) in a separated flask was cooled to −78° C. 2.5M of n-butyllithium in hexane (22.0 mL) was added dropwise. The resulting solution was stirred at −78° C. for 1 hour, and then added via cannula into the solution of the mixed anhydride. The reaction mixture was stirred at −78° C. for 15 minutes, at 0° C. for 30 minutes, then at room temperature overnight. Saturated NHCl (300 mL) was added to quench the reaction. The mixture was extracted with EtOAc (3×200 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by silica gel chromatography, eluting with EtOAc/hexane (0-25%) to give (R)-4-benzyl-3-(2-(5-chlorothiophen-2-yl)acetyl)oxazolidin-2-one (9.43 g, 56%). 1H NMR (CDCl3, 400 MHz) δ 7.33-7.25 (m, 3H), 7.16-7.13 (m, 2H), 6.79-6.76 (m, 2H), 4.70-4.65 (m, 1H), 4.38 (q, J=17.2 Hz, 2H), 4.25-4.18 (m, 2H), 3.27 (dd, J=13.6 Hz, J=3.6 Hz, 1H), 2.77 (dd, J=13.6 Hz, J=3.6 Hz, 1H).

후처리

  1. temperaturere-cooled to −78° C
  2. stirringThe resulting solution was stirred at −78° C. for 1 hour
  3. stirringThe reaction mixture was stirred at −78° C. for 15 minutes, at 0° C. for 30 minutes
  4. customat room temperature
  5. customovernight
  6. additionSaturated NHCl (300 mL) was added
  7. customto quench
  8. customthe reaction
  9. extractionThe mixture was extracted with EtOAc (3×200 mL)
  10. dry with materialThe combined organics were dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified by silica gel chromatography
  14. washeluting with EtOAc/hexane (0-25%)

출처 및 근거

ORD 기록
ord-a79b3bb4a1f3404bbcf4669897456202
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063050B2

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