Lithium Hydroxide → HCID 9987999, compound

HRID 1352869Notes

Reaction equation

HRID 1352869 reaction equation
[CH3:1][C@H:2]([O:11][C:12]1[CH:13]=[C:14](/[CH:18]=[CH:19]/[CH2:20][N:21]2[CH:25]=[CH:24][CH:23]=[C:22]2[C:26]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)=[O:27])[CH:15]=[CH:16][CH:17]=1)[C:3](N1CCOCC1)=[O:4].[OH-:35].[Li+]>O1CCCC1.CO>[CH3:34][C:31]1[CH:32]=[CH:33][C:28]([C:26]([C:22]2[N:21]([CH2:20]/[CH:19]=[CH:18]/[C:14]3[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=3)[O:11][C@@H:2]([CH3:1])[C:3]([OH:4])=[O:35])[CH:25]=[CH:24][CH:23]=2)=[O:27])=[CH:29][CH:30]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 69143363HCID 69143363, compound

Product 1

HCID 9987999HCID 9987999, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (4-methylphenyl)(1-allyl-1H-pyrrol-1-yl)methanone (47.31 g, 210 mmol) in dimethylformamide (650 ml) were added 4-[(2S)-2-(3-iodophenoxy)propanoyl]morpholine (72.24 g, 200 mmol), sodium hydrogencarbonate (33.60 g, 400 mmol), benzyltriethylammonium chloride (45.56 g, 200 mmol) and palladium acetate (2.245 g, 10.0 mmol), and the mixture was stirred for 6 hours at 50–55° C. After the mixture was allowed to cool to room temperature, thereto was added water (1 L) and the mixture was extracted with toluene/ethyl acetate (1/2) twice (1 L and 0.5 L). The organic layer was washed with an aqueous 10% potassium hydrogensulfate solution three times and then water and an aqueous saturated sodium chloride solution. The organic layer was dried over magnesium sulfate. After addition of charcoal, the organic layer was filtered with Celite. The solvent was removed under reduced pressure to give {1-[(2E)-3-(3-{[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]oxy}phenyl)prop-2-enyl]-1H-pyrrol-2-yl}(4-methylphenyl)methanone (about 10 g). To a solution of {1-[(2E)-3-(3-{[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]oxy}phenyl)prop-2-enyl]-1H-pyrrol-2-yl}(4-methylphenyl)methanone (about 100 g) in tetrahydrofuran (350 ml) and methanol (350 ml) was added an aqueous 2N lithium hydroxide solution (500 ml) and the mixture was stirred for 5 hours at 70° C. The reaction mixture was concentrated, followed by addition of water. The mixture was acidified (pH 2–3) with 1N hydrochloric acid. The solution was extracted with toluene/ethyl acetate (1/2)(1 L×2) and dried over anhydrous magnesium sulfate. The solvent was removed and the residue was dried to give (2S)-2-(3-{(1E)-3-[2-(4-methylbenzoyl)-1H-pyrrol-1-yl]prop-1-enyl}phenoxy)propionic acid (about 90 g).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionfollowed by addition of water
  3. extractionThe solution was extracted with toluene/ethyl acetate (1/2)(1 L×2)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was removed
  6. customthe residue was dried

Sources & evidence

ORD record
ord-3ddbb4f74a3b4e749090500963dd5154
Source dataset
uspto-grants-2007_05
Patent number
US07220773B2

Reaction notes

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