Tributylphosphine → 3-{4-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yl)-3-methyl-butoxy]-benzoylamino}-propionic acid methyl ester

HRID 1669315Notes

Reaction equation

HRID 1669315 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]([OH:13])[CH2:9][CH:10]([CH3:12])[CH3:11])[CH:5]=[C:4]([CH3:14])[C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[CH3:56][O:57][C:58](=[O:71])[CH2:59][CH2:60][NH:61][C:62](=[O:70])[C:63]1[CH:68]=[CH:67][C:66](O)=[CH:65][CH:64]=1>C1(C)C=CC=CC=1>[CH3:56][O:57][C:58](=[O:71])[CH2:59][CH2:60][NH:61][C:62](=[O:70])[C:63]1[CH:68]=[CH:67][C:66]([O:13][CH:8]([C:6]2[CH:5]=[C:4]([CH3:14])[C:3]([C:15]3[CH:16]=[CH:17][C:18]([C:21]([F:22])([F:23])[F:24])=[CH:19][CH:20]=3)=[C:2]([CH3:1])[CH:7]=2)[CH2:9][CH:10]([CH3:12])[CH3:11])=[CH:65][CH:64]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 106328533-(4-Hydroxy-benzoylamino)-propionic acid methyl esterHCID 597293931-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yl)-3-methyl-butan-1-ol

Product 1

HCID 673433583-{4-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yl)-3-methyl-butoxy]-benzoylamino}-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 1-(2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-yl)-3-methyl-butan-1-ol (270 mg, 0.8 mmol) in toluene (8 mL) is added 1,1′-(azodicarbonyl) dipiperidine (ADDP, 304 mg, 1.21 mmol) at 0° C., followed by the addition of tributylphosphine (0.3 mL, 12.1 mmol) and 3-(4-hydroxy-benzoylamino)-propionic acid methyl ester (215 mg, 0.96 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 100% of ethyl acetate giving 3-{4-[1-(2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-yl)-3-methyl-butoxy]-benzoylamino}-propionic acid methyl ester. The ester product is taken into methanol (2 mL), treated with sodium hydroxide (5N aqueous, 1 mL) for 5 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 to afford 51 mg of the titled compound. MS (ES): 528.3 [M+H]+.

Workup

  1. washeluted with hexanes with a gradient from 0% of ethyl acetate to 100% of ethyl acetate

Sources & evidence

ORD record
ord-c4e309e9e4d44175acf2708f1cbde33b
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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