Hexane → (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one

HRID 1945047

반응식

HRID 1945047 반응식
[Li]CCCC.CCCCCC.[CH2:12]([C@H:19]1[CH2:23][O:22][C:21](=[O:24])[NH:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:25]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33](Cl)=[O:34])=[CH:27][CH:26]=1>C1COCC1.C(=O)=O.CO>[CH2:12]([C@H:19]1[CH2:23][O:22][C:21](=[O:24])[N:20]1[C:33](=[O:34])[CH2:32][CH2:31][C:28]1[CH:29]=[CH:30][C:25]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[CH:26][CH:27]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

참가 물질

7

반응물 4

HCID 8058HexaneHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 596075633-(Biphenyl-4-yl)propanoyl chloride2회HCID 178418339Butyllithium

생성물 1

HCID 59607884(S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one수율 60.1%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 21973728Carbon dioxide methanol용매

반응 조건

온도
-60.5 °C

실험 절차

To a 1.6 M solution of n-BuLi in hexane (12.1 mL, 19.3 mmol) is added dropwise a solution of (S)-(−)-4-benzyl-2-oxazolidinone (3.26 g, 18.4 mmol) in dry THF (80 mL) at −71.6° C. under nitrogen over 10 minutes. The solution is warmed up to −60.5° C. while the addition, and allowed to stir for 1 hour in dry ice/MeOH bath. 3-(Biphenyl-4-yl)propanoyl chloride (intermediate 13: 5.46 g, 22.31 mmol) in dry THF (20 mL) is added dropwise at −72° C. over 5 minutes. The solution is warmed up to −56.5° C. while the addition. After stirring 10 minutes at the same temperature, the reaction mixture is allowed to warm to room temperature and stirring is continued for 3 hours. The reaction mixture is filtered, and the collected precipitate is washed with 20 mL (10 mL×2) of MeOH and then with 150 mL of H2O to give the desired product (4.26 g). The products in the mother liquor is extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is suspended in 80 mL of MeOH, and the suspension is filtered and washed with 20 mL of MeOH (1.79 g). The two fractions are mixed to give (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one (6.05 g, 85% in 2 steps). Retention time=1.77 minutes (condition A); MS (m+1)=387.3; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.77 (dd, J=13.39, 9.35 Hz, 1H) 2.99-3.15 (m, 2H) 3.20-3.43 (m, 3H) 4.09-4.24 (m, 2H), 4.68 (dddd, J=9.76, 6.73, 3.47, 3.28 Hz, 1H) 7.18 (d, J=7.07 Hz, 2H) 7.23-7.37 (m, 6H) 7.42 (t, J=7.58 Hz, 2H) 7.53 (d, J=8.1 Hz, 2H), 7.57 (d, J=7.8 Hz, 2H).

후처리

  1. temperatureThe solution is warmed up to −56.5° C. while the addition
  2. temperatureto warm to room temperature
  3. stirringstirring
  4. waitis continued for 3 hours
  5. filtrationThe reaction mixture is filtered
  6. washthe collected precipitate is washed with 20 mL (10 mL×2) of MeOH

출처 및 근거

ORD 기록
ord-631e5ae675e74b0c8e3e4b214b5bf57f
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08394853B2

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