Citric Acid → (S)-3-(Isoxazol-3-yl)-3-(4-((4-methyl-2-(4-chlorophenyl)thiazol-5-yl)methoxy)phenyl)propanoic acid

HRID 1675301ノート

反応式

HRID 1675301 の反応式
[C:1](=[O:4])([O-])[O-:2].[Cs+].[Cs+].C([C@H]1COC(=O)N1C(=O)[CH2:21][C@@H:22]([C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=1)[C:23]1[CH:27]=[CH:26][O:25][N:24]=1)C1C=CC=CC=1.Cl[CH2:37][C:38]1[S:42][C:41]([C:43]2[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=2)=[N:40][C:39]=1[CH3:50].OO.[Li+].[OH-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O.CCOC(C)=O.C1COCC1.O>[O:25]1[CH:26]=[CH:27][C:23]([C@H:22]([C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:37][C:38]3[S:42][C:41]([C:43]4[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=4)=[N:40][C:39]=3[CH3:50])=[CH:32][CH:33]=2)[CH2:21][C:1]([OH:2])=[O:4])=[N:24]1

参加物

11

反応物 6

HCID 311Citric AcidHCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 27636945-(Chloromethyl)-2-(4-chlorophenyl)-4-methyl-1,3-thiazoleHCID 57801829(S)-4-Benzyl-3-((S)-3-(4-hydroxyphenyl)-3-(isoxazol-3-yl)propanoyl)oxazolidin-2-one

生成物 1

HCID 59300642(S)-3-(Isoxazol-3-yl)-3-(4-((4-methyl-2-(4-chlorophenyl)thiazol-5-yl)methoxy)phenyl)propanoic acid

試薬・触媒・溶媒 4

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

Cesium carbonate (170 mg, 0.52 mmol) was added to a mixture of 7.5 (140 mg, 0.36 mmol) and 5-(chloromethyl)-4-methyl-2-(4-chlorophenyl)thiazole (110 mg, 0.43 mmol, commercially available from Bionet Research Intermediates, UK) in DMSO (3 mL). The resulting mixture was stirred at room temperature for 2 hours. The mixture was treated with EtOAc (25 mL) and water (15 mL). The organic layer was separated, washed twice with brine, dried, and concentrated. The crude product (210 mg, 0.32 mmol) was treated with THF (3 mL) and hydrogen peroxide (35 wt %, 1.0 mL) and cooled to 0° C. Aqueous LiOH (2.0 M, 1.0 mL, 2.0 mmol) was added. The resulting mixture was stirred at 0° C. for 10 minutes and then at room temperature for 2 Hours. The crude mixture LCMS analysis showed reaction to complete. The mixture was diluted with EtOAc (50 mL) and 5 mL of aqueous citric acid (0.5 M, 2.5 mmol) was added. The mixture was washed with water. The organic layer was separated, and concentrated under reduced pressure. The residue was purified by reverse phase prep HPLC (5-95% water-MeCN, gradient, with 0.1% TFA). The desired fraction was collected and treated by lyophilizing to give 57 (21 mg) as a white powder. MS API-ES m/e: 453 (M−H). 1H NMR (500 MHz) (CDCl3) δ 8.33 (1H, s); 7.93 (2H, d, J=10Hz); 7.49 (2H, d, J=5Hz); 7.25 (2H, d, J=5 Hz); 6.95 (2H, d, J=10Hz); 6.11 (1H, s); 5.19 (2H, s); 4.60 (1H, m); 3.38 (1H, m), 3.03 (1H, m), 2.57 (3H, s).

後処理

  1. customThe organic layer was separated
  2. washwashed twice with brine
  3. customdried
  4. concentrationconcentrated
  5. temperaturecooled to 0° C
  6. stirringThe resulting mixture was stirred at 0° C. for 10 minutes
  7. customat room temperature
  8. customreaction
  9. additionwas added
  10. washThe mixture was washed with water
  11. customThe organic layer was separated
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by reverse phase prep HPLC (5-95% water-MeCN, gradient, with 0.1% TFA)
  14. customThe desired fraction was collected
  15. additiontreated

出典と根拠

ORDレコード
ord-34d507920d294a169d5b5d3d33add93b
出典データセット
uspto-grants-2011_08
特許番号
US08003648B2

反応ノート

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