Diisopropylethylamine → 3-{4-[1-Allyl-1-(4'-trifluoromethyl-biphenyl-4-yloxymethyl)-but-3-enyl]-benzoylamino}-propionic acid methyl ester

HRID 658295Notes

Reaction equation

HRID 658295 reaction equation
[CH2:1]([C:4]([C:26]1[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[CH:28][CH:27]=1)([CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)[CH2:5][CH:6]=[CH2:7])[CH:2]=[CH2:3].Cl.[NH2:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40].O.ON1C2C=CC=C[C:47]=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O>[CH3:47][O:40][C:39](=[O:41])[CH2:38][CH2:37][NH:36][C:30](=[O:32])[C:29]1[CH:33]=[CH:34][C:26]([C:4]([CH2:5][CH:6]=[CH2:7])([CH2:8][O:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:17]=[CH:18][C:19]([C:22]([F:23])([F:24])[F:25])=[CH:20][CH:21]=3)=[CH:14][CH:15]=2)[CH2:1][CH:2]=[CH2:3])=[CH:27][CH:28]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 12201475beta-Alanine HydrochlorideHCID 674861864-[1-Allyl-1-(4'-trifluoromethyl-biphenyl-4-yloxymethyl)-but-3-enyl]-benzoic acid

Product 1

HCID 674857653-{4-[1-Allyl-1-(4'-trifluoromethyl-biphenyl-4-yloxymethyl)-but-3-enyl]-benzoylamino}-propionic acid methyl esterYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-[1-allyl-1-(4′-trifluoromethyl-biphenyl-4-yloxymethyl)-but-3-enyl]-benzoic acid (0.044 g, 0.094 mmol), beta-alanine, hydrochloride salt (0.0189 g, 0.135 mmol), and 1-hydroxybenzotriazole hydrate (0.0193 g, 0.143 mmol) in DMF (2.0 mL) is treated with N,N-diisopropylethylamine (0.0480 mL, 0.275 mmol), then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.0278 g, 0.145 mmol) and stirred overnight. The reaction mixture is diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The combined organic extracts are washed with water, brine, dried over MgSO4, filtered, and concentrated. The residue is loaded onto silica gel and eluted with hexanes using a gradient of 10% EtOAc to 75% EtOAc to provide 0.0298 g (58%) of the title compound as a clear film. MS (ES): 552.2 [M+H]−.

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. washThe combined organic extracts are washed with water, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted with hexanes using a gradient of 10% EtOAc to 75% EtOAc

Sources & evidence

ORD record
ord-0f6bb00c2077474ab2bc682e06a3c2d5
Source dataset
uspto-grants-2011_12
Patent number
US08076374B2

Reaction notes

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