Sodium Hydroxide → 3-{4-[6-(4-Trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-benzoylamino}-propionic acid

HRID 1669251Notes

Reaction equation

HRID 1669251 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][CH2:5][NH:6][C:7](=[O:32])[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:17]=[N:18][C:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=3)=[CH:20][CH:21]=2)=[CH:10][CH:9]=1.[OH-].[Na+]>C(O)C>[F:30][C:28]([F:29])([F:31])[C:25]1[CH:24]=[CH:23][C:22]([C:19]2[N:18]=[CH:17][C:16]([CH2:15][O:14][C:11]3[CH:12]=[CH:13][C:8]([C:7]([NH:6][CH2:5][CH2:4][C:3]([OH:33])=[O:2])=[O:32])=[CH:9][CH:10]=3)=[CH:21][CH:20]=2)=[CH:27][CH:26]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 673435223-{4-[6-(4-Trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-benzoylamino}-propionic acid methyl ester

Product 1

HCID 115031783-{4-[6-(4-Trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-benzoylamino}-propionic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of [6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-methanol (120 mg, 0.47 mmol) in THF (2 mL) and toluene (4 mL) is added 1,1′-(azodicarbonyl)dipiperidine (ADDP, 179.5 mg, 0.71 mmol) at 0° C., followed by the addition of tributylphosphine (0.18 mL, 0.71 mmol) and 3-(4-hydroxy-benzoylamino)-propionic acid methyl ester (127 mg, 0.57 mmol). The reaction mixture is warmed up to room temperature and stirred overnight. The mixture is loaded on silica gel, eluted with hexanes with a gradient from 0% of ethyl acetate to 50% of ethyl acetate giving 3-{4-[6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-benzoylamino}-propionic acid methyl ester. The ester product is taken into ethanol (2 mL), treated with sodium hydroxide (5N aqueous, 1 mL) for 3 h at room temperature. The mixture is concentrated, diluted with ethyl acetate, acidified with 5 N HCl (1.1 mL), extracted with ethyl acetate. The organic layers are dried and concentrated giving 3-{4-[6-(4-Trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-benzoylamino}-propionic acid (33 mg). MS (ES): 443.2 [M+H]−.

Workup

  1. concentrationThe mixture is concentrated
  2. additiondiluted with ethyl acetate
  3. extractionextracted with ethyl acetate
  4. customThe organic layers are dried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a22eb17e657c4cab97b835bcfdcfc775
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

Loading…