Potassium Carbonate → 2-{2-Butyl-5-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy)-2-methylpropionic acid

HRID 1609975ノート

反応式

HRID 1609975 の反応式
C(OC(=O)C(OC1C=C(O)C=CC=1CCCC)(C)C)C.CC1OC(C2C=CC=CC=2)=NC=1CCOS(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].C([O:54][C:55](=[O:85])[C:56]([O:59][C:60]1[CH:65]=[C:64]([O:66][CH2:67][CH2:68][C:69]2[N:70]=[C:71]([C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)[O:72][C:73]=2[CH3:74])[CH:63]=[CH:62][C:61]=1[CH2:81][CH2:82][CH2:83][CH3:84])([CH3:58])[CH3:57])C.[OH-].[Na+]>C(O)C>[CH2:81]([C:61]1[CH:62]=[CH:63][C:64]([O:66][CH2:67][CH2:68][C:69]2[N:70]=[C:71]([C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)[O:72][C:73]=2[CH3:74])=[CH:65][C:60]=1[O:59][C:56]([CH3:57])([CH3:58])[C:55]([OH:85])=[O:54])[CH2:82][CH2:83][CH3:84]

参加物

7

反応物 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 120517392-(5-Methyl-2-phenyloxazol-4-yl)ethyl 4-methylbenzenesulfonateHCID 693102962-{2-Butyl-5-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid ethyl esterHCID 693120282-(2-Butyl-5-hydroxyphenoxy)-2-methylpropionic acid ethyl ester

生成物 1

HCID 222611622-{2-Butyl-5-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy)-2-methylpropionic acid収率 49%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
55 °C

実験手順

The following example exemplifies the general procedure for the parallel synthesis of analogs utilizing the DynaVac carousel. To a 50 mL glass tube with screw cap and nitrogen inlet were charged 2-(2-butyl-5-hydroxyphenoxy)-2-methylpropionic acid ethyl ester, (0.050 g, 0.178 mmol), toluene-4-sulfonic acid 2-(5-methyl-2-phenyloxazol-4-yl)ethyl ester (0.067 g, 0.187 mmol), and powdered potassium carbonate (0.050 g, 0.36 mmol) in 1 mL of absolute ethanol. The mixture was heated to reflux for 18 h. MS analysis of the reaction indicated that 2-{2-Butyl-5-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid ethyl ester, MS (ES) m/e 466 (M+1) had formed. Next 0.4 mL of 5N sodium hydoxide was added and the reaction was heated for 3 h at 55° C. The ethanol was removed in vacuo and the residue was treated with 1 mL of 5N hydrochloric acid and 1 mL of dichloromethane and poured into a 3 mL ChemElute column to remove the aqueous layer. The column was eluted with additional dichloromethane until nothing UV active remained on the column. The solvent was removed in vaco. The crude residue was purified by mass-directed reverse phase HPLC to provide 0.038 g (49%) of 2-{2-Butyl-5-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid, 1H NMR (400 MHz, CDCl3) δ 7.99 (dd, J=6.4, 2.4 Hz, 2H), 7.46 (dd, J=5.9, 2.4 Hz, 3H), 7.03 (d, J=8.3 Hz, 1H), 6.62 (d, J=2.4 Hz, 1H), 6.51 (dd, J=8.3, 2.4 Hz, 1H), 4.18 (t, J=7.3 Hz, 2H), 2.95 (t, J=7.3 Hz, 2H), 2.54 (t, J=7.6 Hz, 2H), 2.38 (s, 3H), 1.63 (s, 6H), 1.53 (quintet, J=7.6 Hz, 2H), 1.35 (sextet, J=7.3 Hz, 2H), 0.92 (t, J=7.1 Hz, 3H), MS (ES) m/e 438 (M+1). The following compounds were also prepared by this procedure: 2-{2-Butyl-5-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid ethyl ester, MS (ES) m/e 472 (M+1). Example 34A: 2-{2-Butyl-5-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid

後処理

  1. customfor the parallel synthesis of analogs
  2. customTo a 50 mL glass tube with screw cap
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 18 h
  5. customMS (ES) m/e 466 (M+1) had formed
  6. customThe ethanol was removed in vacuo
  7. additionthe residue was treated with 1 mL of 5N hydrochloric acid and 1 mL of dichloromethane
  8. additionpoured into a 3 mL ChemElute column
  9. customto remove the aqueous layer
  10. washThe column was eluted with additional dichloromethane until nothing UV
  11. customThe solvent was removed in vaco
  12. customThe crude residue was purified by mass-directed reverse phase HPLC

出典と根拠

ORDレコード
ord-337da601104a4828903d96863da39530
出典データセット
uspto-grants-2006_01
特許番号
US06982278B2

反応ノート

読み込み中…