Methylparaben → Ethyl 4-{1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-heptyloxy}-benzoate

HRID 1669252Notes

Reaction equation

HRID 1669252 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[CH:13][C:12]([CH:15]([OH:22])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.N(C(N1CCCCC1)=O)=N[C:27](N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.O[C:57]1[CH:66]=[CH:65][C:60]([C:61]([O:63][CH3:64])=[O:62])=[CH:59][CH:58]=1>C1COCC1.C1(C)C=CC=CC=1>[F:24][C:2]([F:23])([F:1])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:14]=[CH:13][C:12]([CH:15]([O:22][C:57]3[CH:66]=[CH:65][C:60]([C:61]([O:63][CH2:64][CH3:27])=[O:62])=[CH:59][CH:58]=3)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 7456MethylparabenHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 597294261-[6-(4-Trifluoromethyl-phenyl)-pyridin-3-yl]-heptan-1-ol

Product 1

HCID 67341864Ethyl 4-{1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-heptyloxy}-benzoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-heptan-1-ol (280 mg, 0.83 mmol) in THF (2 mL) and toluene (4 mL) is added 1,1′-(azodicarbonyl)dipiperidine (ADDP, 314.1 mg, 1.24 mmol) at 0° C., followed by the addition of tributylphosphine (0.31 mL, 1.24 mmol) and methyl 4-hydroxybenzoate (151.5 mg, 1 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 ethyl 4-{1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-heptyloxy}-benzoate. 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 4-{1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-heptyloxy}-benzoic acid (330 mg).

Workup

  1. washeluted with hexanes with a gradient from 0% of ethyl acetate to 50% of ethyl acetate

Sources & evidence

ORD record
ord-fc100a9098ee4ab585768ddf1a62b0e8
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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