3-(4-Hydroxyphenyl)propionic acid → N-(2,4-difluorobenzyl)-3-(4-hydroxyphenyl)-N-propylpropanamide

HRID 899893Notes

Reaction equation

HRID 899893 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.[F:13][C:14]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:15]=1[CH2:16][NH:17][CH2:18][CH2:19][CH3:20].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[F:13][C:14]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:15]=1[CH2:16][N:17]([CH2:18][CH2:19][CH3:20])[C:10](=[O:12])[CH2:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=1

Participants

7

Reactant 5

HCID 103943-(4-Hydroxyphenyl)propionic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 24690356[(2,4-Difluorophenyl)methyl](propyl)amine

Product 1

HCID 69120491N-(2,4-difluorobenzyl)-3-(4-hydroxyphenyl)-N-propylpropanamideYield 68.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(4-Hydroxyphenyl)propionic acid (245 mg, 1.474 mmol) in DMF (5 ml) was cooled in an ice-bath. N-(2,4-Difluorobenzyl)-N-propylamine (300.4 mg, 1.622 mmol) was added and then TBTU (521 mg, 1.622 mmol) followed by DIPEA (400 mg, 3.096 mmol). The mixture was stirred at room temperature overnight. Sodium hydrogencarbonate aqueous solution (sat.) was added. The mixture was extracted with ethyl acetate (×2). The extracts were combined and dried (magnesium sulphate) and evaporated. Chromatography of the residue on a column (ISOLUTE® SI, 5 g/25 ml) using DCM/heptane (50:50), DCM and then MeOH/DCM (1:99, then 2:98) as eluant gave 336 mg the desired product, yield 68%.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (×2)
  2. dry with materialdried (magnesium sulphate)
  3. customevaporated

Sources & evidence

ORD record
ord-3ce818fdfd1441a98695c0d1f53b0c77
Source dataset
uspto-grants-2008_04
Patent number
US07355069B2

Reaction notes

Loading…