Sodium Hydroxide → 4-{2-(2-Carboxy-ethyl)-3-[6-(3-methanesulfonyl-5-thiazol-2-yl-phenoxy)-hexyl]-phenoxy}-butyric Acid

HRID 418067Notes

Reaction equation

HRID 418067 reaction equation
C([O:3][C:4](=[O:40])[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](I)[CH:23]=2)[C:10]=1[CH2:33][CH2:34][C:35]([O:37]CC)=[O:36])C.C([Sn](CCCC)(CCCC)[C:46]1[S:47][CH:48]=[CH:49][N:50]=1)CCC.[OH-].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:35]([CH2:34][CH2:33][C:10]1[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:23]=[C:24]([C:46]3[S:47][CH:48]=[CH:49][N:50]=3)[CH:25]=[C:26]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:27]=2)=[CH:12][CH:13]=[CH:14][C:9]=1[O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:3])=[O:40])([OH:37])=[O:36]

Participants

8

Reactant 3

HCID 14798Sodium HydroxideHCID 27632592-(Tributylstannyl)-1,3-thiazoleHCID 578630374-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric Acid Ethyl Ester

Product 1

HCID 578631184-{2-(2-Carboxy-ethyl)-3-[6-(3-methanesulfonyl-5-thiazol-2-yl-phenoxy)-hexyl]-phenoxy}-butyric Acid

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
110 °C

Procedure

To a solution containing 4-{2-(2-ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric acid ethyl ester (90 mg, 0.14 mmol) and 2-(tributylstannyl)thiazole (0.088 mL, 0.28 mmol) in toluene (4 mL) was added Pd(PPh3)4 (8 mg, 5 mol %). The reaction mixture was stirred at 110° C. for 12 h, then diluted with EtOAc. The resulting solution was washed with brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford a crude sample which was dissolved in hot ethanol (4 mL). To this solution, 1 N sodium hydroxide (1 mL) was added and the reaction mixture was stirred at 60° C. for 3 h. Once the hydrolysis was completed as determined by LCMS, the reaction mixture was diluted with EtOAc and washed with 10% HCl and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford a crude sample which was purified by preparative HPLC. HR-ES(+) m/e calcd for C29H35NO8S2 (M+H)+ 590.1877, found 590.1876.

Workup

  1. washThe resulting solution was washed with brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford a crude sample which
  5. stirringthe reaction mixture was stirred at 60° C. for 3 h
  6. washwashed with 10% HCl and brine
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto afford a crude sample which
  10. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-28e298c860d64643a658ddb31cf1dcb8
Source dataset
uspto-grants-2012_01
Patent number
US08093253B2

Reaction notes

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