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Cesium carbonate → (S)-2-(4-{2-[5-Methyl-2-(5-methyl-thiophen-2-yl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-butyric Acid Ethyl Ester

HRID 585266
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HRID 585266 반응식
[CH2:1]([O:3][C:4](=[O:22])[C@@:5]([CH3:21])([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH3:2].[CH3:23][C:24]1[O:28][C:27]([C:29]2[S:30][C:31]([CH3:34])=[CH:32][CH:33]=2)=[N:26][C:25]=1[CH2:35][CH2:36]OS(C1C=CC(C)=CC=1)(=O)=O.[C:48]([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:22])[C@:5]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:36][CH2:35][C:25]2[N:26]=[C:27]([C:29]3[S:30][C:31]([CH3:34])=[CH:32][CH:33]=3)[O:28][C:24]=2[CH3:23])=[CH:9][CH:8]=1)([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:21][CH3:48])[CH3:2]
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참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 60024296(S)-3-(4-hydroxyphenyl)-2-methyl-2-phenoxypropionic acid ethyl esterHCID 86592426Toluene-4-sulfonic acid 2-[5-methyl-2-(5-methyl-thiophen-2-yl)-oxazol-4-yl]ethyl ester

생성물 1

HCID 69316116(S)-2-(4-{2-[5-Methyl-2-(5-methyl-thiophen-2-yl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-butyric Acid Ethyl Ester수율 47%

시약·촉매·용매 2

HCID 6228
Dimethylformamide
용매
HCID 8857Ethyl Acetate용매

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온도
55 °C

실험 절차

(S)-3-(4-Hydroxyphenyl)-2-methyl-2-phenoxypropionic acid ethyl ester (255 mg, 0.85 mmol), toluene-4-sulfonic acid 2-[5-methyl-2-(5-methyl-thiophen-2-yl)-oxazol-4-yl]ethyl ester (383 mg, 1.02 mmol) and Cs2CO3 (335 mg, 1.02 mmol) are combined in anhydrous DMF (6 mL) and stirred for 16 h at 55° C. under an atmosphere of nitrogen. The mixture was then cooled and diluted with ethyl acetate (50 mL), and washed with water then brine. The organic layer was dried with MgSO4 and concentrated in vacuo to a viscous tan oil. The residue was purified by flash column chromatography (200 g silica, hexanes to 25% EtOAc/hexanes) to provide the title compound as a colorless oil (201 mg, 47%). 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J=3.4 Hz, 1H), 7.22-7.13 (m, 4H), 6.97 (t, J=7.2 Hz, 1H), 6.85-6.80 (m, 4H), 6.72 (dd, J=3.6, 1.2 Hz, 1H), 4.23-4.17 (m, 4H), 3.26 (A of Abq, J=13.6 Hz, 1H), 3.11 (B of Abq, J=13.6 Hz, 1H), 2.94 (t, J=5.6 Hz, 2H), 2.50 (s, 3H), 2.34 (s, 3H), 1.39 (s, 3H), 1.22 (t, J=7.2 Hz, 3H); MS (EI+) 505.9 (M+H); 637.8 (M+H+Cs).

후처리

  1. temperatureThe mixture was then cooled
  2. washwashed with water
  3. dry with materialThe organic layer was dried with MgSO4
  4. concentrationconcentrated in vacuo to a viscous tan oil
  5. customThe residue was purified by flash column chromatography (200 g silica, hexanes to 25% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-a8348473a0534c8b902fc2c908b526a6
출처 데이터셋
uspto-grants-2005_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06930120B2

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