Triphenylphosphine → 3-{6-Hydroxymethyl-3-[8(4-methoxyphenyl)octyloxy]pyridin-2-yl}propenoic Acid

HRID 1753

Reaction equation

HRID 1753 reaction equation
Br[C:2]1[C:7]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[CH:6][CH:5]=[C:4]([CH2:25][OH:26])[N:3]=1.C([O-])(=O)C.[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:51]([O-:55])(=[O:54])[CH:52]=[CH2:53].[K+]>CN(C=O)C.O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.[Pd](Cl)Cl>[OH:26][CH2:25][C:4]1[N:3]=[C:2]([CH:53]=[CH:52][C:51]([OH:55])=[O:54])[C:7]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[CH:6][CH:5]=1

Participants

9

Reactant 4

HCID 11776TriphenylphosphineHCID 517044Potassium AcetateHCID 4429391Potassium acrylate2×HCID 196927112-Bromo-6-hydroxymethyl-[8(4-methoxyphenyl)octyloxy]pyridine

Product 1

HCID 540218973-{6-Hydroxymethyl-3-[8(4-methoxyphenyl)octyloxy]pyridin-2-yl}propenoic Acid

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-bromo-6-hydroxymethyl-[8(4-methoxyphenyl)octyloxy]pyridine (5.00 g, 11.8 mmol) in DMF (22.8 ml) and water (1.2 ml) were added potassium acetate (2.91 g, 29.7 mmol), tetra-n-butylammonium iodide (4.37 g, 11.8 mmol); triphenylphosphine (0.245 g, 0.94 mmol), palladium chloride (83 mg, 0.47 mmol) and potassium acrylate (3.91 g, 35.4 mmol). The mixture was placed under nitrogen and stirred and heated at 120° C. for 3.3 h. Some potassium acrylate remained undissolved. The mixture was cooled, solids filtered and washed with ethyl acetate (2×60 ml). The filtrate was washed with water (250 ml) and with 5% sodium chloride solution (2×125 ml). The organic layer was dried and evaporated. The pure product was obtained by flash column chromatography (silica, 20% ether in dichloromethane) (3.52 g, 72%). mp 112°-114° C.

Workup

  1. temperatureThe mixture was cooled
  2. filtrationsolids filtered
  3. washwashed with ethyl acetate (2×60 ml)
  4. washThe filtrate was washed with water (250 ml) and with 5% sodium chloride solution (2×125 ml)
  5. customThe organic layer was dried
  6. customevaporated
  7. customThe pure product was obtained by flash column chromatography (silica, 20% ether in dichloromethane) (3.52 g, 72%)

Sources & evidence

ORD record
ord-d167806c04b646d4b1c49664d0f6f7f3
Source dataset
uspto-grants-1998_03
Patent number
US05726315

Linked notes

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