Sodium Hydroxide → 4-[3-[6-(3-Benzo[1,3]dioxol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-carboxy-ethyl)-phenoxy]-butyric acid

HRID 418081Notes

Reaction equation

HRID 418081 reaction equation
C([O:3][C:4](=[O:48])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:25]=[C:24]([C:32]3[CH:40]=[CH:39][C:35]4[O:36][CH2:37][O:38][C:34]=4[CH:33]=3)[CH:23]=2)[C:10]=1[CH2:41][CH2:42][C:43]([O:45]CC)=[O:44])C.[OH-].[Na+]>C1COCC1.C(O)C.C(#N)C>[O:36]1[C:35]2[CH:39]=[CH:40][C:32]([C:24]3[CH:23]=[C:22]([CH:27]=[C:26]([S:28]([CH3:31])(=[O:29])=[O:30])[CH:25]=3)[O:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][C:11]3[C:10]([CH2:41][CH2:42][C:43]([OH:45])=[O:44])=[C:9]([CH:14]=[CH:13][CH:12]=3)[O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:48])=[O:3])=[CH:33][C:34]=2[O:38][CH2:37]1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 578630894-[3-[6-(3-Benzo[1,3]dioxol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

Product 1

HCID 441995894-[3-[6-(3-Benzo[1,3]dioxol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-carboxy-ethyl)-phenoxy]-butyric acidYield 80.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
47.5 °C

Procedure

To a solution of the 4-[3-[6-(3-benzo[1,3]dioxol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (26.7 g, 39.1 mmol) in THF (200 mL) and ethanol (200 mL) was added aqueous 1.0 N sodium hydroxide (200 mL) at room temperature. The resulting suspension was heated to 45-50° C. and the mixture was stirred for 30 min and then cooled to room temperature and stirred for 15 h at which time TLC analysis of the mixture indicated the absence of starting material. Then, the reaction mixture was concentrated and the residue was diluted with water (200 mL) and extracted with diethyl ether (150 mL) to remove any neutral impurities. The aqueous layer was acidified with 1.0 N hydrochloric acid and the precipitated white organic compound was extracted into ethyl acetate (2×200 mL). The combined ethyl acetate extracts were washed with brine solution (300 mL) and the organic layers were dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent afforded the crude product which was dissolved in acetonitrile (270 mL) at hot condition and was stored in the refrigerator. The resulting white solids were collected by filtration and washed with acetonitrile. After air-drying, 4-[3-[6-(3-benzo[1,3]dioxol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-carboxy-ethyl)-phenoxy]-butyric acid (19.7 g, 80.5%) was isolated as a white solid. ES(+)-HRMS m/e calcd for C33H38O10S (M+Na)+ 649.2078, found 649.2076.

Workup

  1. temperaturecooled to room temperature
  2. stirringstirred for 15 h at which time TLC analysis of the mixture
  3. concentrationThen, the reaction mixture was concentrated
  4. additionthe residue was diluted with water (200 mL)
  5. extractionextracted with diethyl ether (150 mL)
  6. customto remove any neutral impurities
  7. extractionthe precipitated white organic compound was extracted into ethyl acetate (2×200 mL)
  8. washThe combined ethyl acetate extracts were washed with brine solution (300 mL)
  9. dry with materialthe organic layers were dried over anhydrous magnesium sulfate
  10. filtrationFiltration of the drying agent and removal of the solvent
  11. customafforded the crude product which
  12. filtrationThe resulting white solids were collected by filtration
  13. washwashed with acetonitrile
  14. customAfter air-drying

Sources & evidence

ORD record
ord-309a07f0ce2a4ce690aa7b7f68fa1370
Source dataset
uspto-grants-2012_01
Patent number
US08093253B2

Reaction notes

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