Potassium Carbonate → 2-{5-[2-(2-Biphenyl-3-yl-5-methyloxazol-4-yl)ethoxy]-2-butylphenoxy}-2-methylpropionic acid

HRID 398188Notes

Reaction equation

HRID 398188 reaction equation
C(OC(=O)C(OC1C=C(O)C=CC=1CCCC)(C)C)C.C(=O)([O-])[O-].[K+].[K+].C([O:29][C:30](=[O:66])[C:31]([O:34][C:35]1[CH:40]=[C:39]([O:41][CH2:42][CH2:43][C:44]2[N:45]=[C:46]([C:50]3[CH:51]=[C:52]([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)[CH:53]=[CH:54][CH:55]=3)[O:47][C:48]=2[CH3:49])[CH:38]=[CH:37][C:36]=1[CH2:62][CH2:63][CH2:64][CH3:65])([CH3:33])[CH3:32])C.[OH-].[Na+]>C(O)C>[C:52]1([C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=2)[CH:53]=[CH:54][CH:55]=[C:50]([C:46]2[O:47][C:48]([CH3:49])=[C:44]([CH2:43][CH2:42][O:41][C:39]3[CH:38]=[CH:37][C:36]([CH2:62][CH2:63][CH2:64][CH3:65])=[C:35]([CH:40]=3)[O:34][C:31]([CH3:32])([CH3:33])[C:30]([OH:66])=[O:29])[N:45]=2)[CH:51]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693120282-(2-Butyl-5-hydroxyphenoxy)-2-methylpropionic acid ethyl esterHCID 698723832-{5-[2-(2-Biphenyl-3-yl-5-methyloxazol-4-yl)ethoxy]-2-butylphenoxy}-2-methylpropionic acid ethyl ester

Product 1

HCID 226335092-{5-[2-(2-Biphenyl-3-yl-5-methyloxazol-4-yl)ethoxy]-2-butylphenoxy}-2-methylpropionic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
55 °C

Procedure

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) (see Example 41, Part B), toluene-4-sulfonic acid 2-(5-methyl-2-bipheny-3-yl-loxazol-4-yl)ethyl ester (0.187 mmol) (see Ex. 22, part B), 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-{5-[2-(2-biphenyl-3-yl-5-methyloxazol-4-yl)ethoxy]-2-butylphenoxy}-2-methylpropionic acid ethyl ester, MS (ES) m/e 542 (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 vacuo. The crude residue was purified by mass-directed reverse phase HPLC to provide 2-{5-[2-(2-biphenyl-3-yl-5-methyloxazol-4-yl)ethoxy]-2-butylphenoxy}-2-methylpropionic acid. 1H NMR (400 MHz, CDCl3) δ8.27 (s, 1H), 7.95 (d, J=7.8 Hz, 1H), 7.70-7.68 (m, 3H), 7.53 (t, J=7.8 Hz, 1H), 7.46 (t, J=7.6 Hz, 2H), 7.38 (t, J=7.3 Hz, 1H), 7.04 (d, J=8.3 Hz, 1H), 6.72 (d, J=2.0 Hz, 1H), 6.53 (dd, J=8.3, 2.4Hz, 1H), 4.20 (t, J=7.8 Hz, 2H), 2.94 (t, J=7.8 Hz, 2H), 2.56 (t, J=7.8 Hz, 2H), 2.38 (s, 3H), 1.64 (s, 6H), 1.54 (quintet, J=7.5 Hz, 2H), 1.35 (sextet, J=7.3 Hz, 2H), 0.93 (t, J=7.3 Hz, 3H), MS (ES) m/e 514 (M+1).

Workup

  1. customTo a 50 mL glass tube with screw cap
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 18 h
  4. customMS (ES) m/e 542 (M+1) had formed
  5. customThe ethanol was removed in vacuo
  6. additionthe residue was treated with 1 mL of 5N hydrochloric acid and 1 mL of dichloromethane
  7. additionpoured into a 3 mL ChemElute column
  8. customto remove the aqueous layer
  9. washThe column was eluted with additional dichloromethane until nothing UV
  10. customThe solvent was removed in vacuo
  11. customThe crude residue was purified by mass-directed reverse phase HPLC

Sources & evidence

ORD record
ord-80bf943ba472436a84eb992d33b64af3
Source dataset
uspto-grants-2003_08
Patent number
US06610696B2

Reaction notes

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