Diisopropylethylamine → 3-{4-[1-Allyl-1-(2,6-dimethyl-4'-trifluoromethyl-biphenyl-4-yloxymethyl)-but-3-enyl]-benzoylamino}-propionic acid methyl ester

HRID 658298Notes

Reaction equation

HRID 658298 reaction equation
[CH2:1]([C:4]([C:28]1[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=1)([CH2:8][O:9][C:10]1[CH:15]=[C:14]([CH3:16])[C:13]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)=[C:12]([CH3:27])[CH:11]=1)[CH2:5][CH:6]=[CH2:7])[CH:2]=[CH2:3].Cl.[CH3:38][O:39][C:40](=[O:44])[CH2:41][CH2:42][NH2:43].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O>[CH3:38][O:39][C:40](=[O:44])[CH2:41][CH2:42][NH:43][C:32](=[O:33])[C:31]1[CH:30]=[CH:29][C:28]([C:4]([CH2:1][CH:2]=[CH2:3])([CH2:8][O:9][C:10]2[CH:15]=[C:14]([CH3:16])[C:13]([C:17]3[CH:18]=[CH:19][C:20]([C:23]([F:24])([F:26])[F:25])=[CH:21][CH:22]=3)=[C:12]([CH3:27])[CH:11]=2)[CH2:5][CH:6]=[CH2:7])=[CH:36][CH:35]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 684894364-[1-Allyl-1-(2,6-dimethyl-4'-trifluoromethyl-biphenyl-4-yloxymethyl)-but-3-enyl]-benzoic acid

Product 1

HCID 674863613-{4-[1-Allyl-1-(2,6-dimethyl-4'-trifluoromethyl-biphenyl-4-yloxymethyl)-but-3-enyl]-benzoylamino}-propionic acid methyl esterYield 72.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-[1-allyl-1-(2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-yloxymethyl)-but-3-enyl]-benzoic acid (0.349 g, 0.705 mmol), 3-amino-propionic acid methyl ester hydrochloride (0.112 g, 0.804 mmol), and 1-hydroxybenzotriazole hydrate (HOBt, 0.121 g, 0.898 mmol) in DMF (7.0 mL) is added N,N-diisopropylethylamine (0.38 mL, 2.2 mmol), then N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI, 0.180 g, 0.938 mmol) and stirred overnight. The reaction mixture is poured into water (25 mL) and extracted with EtOAc (3×25 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 using hexanes with an ethyl acetate gradient from 0% to 75% to provide 0.296 g (72%) of the title compound as a white foam. MS (ES): 580.4 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×25 mL)
  2. washThe combined organic extracts are washed with water, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted

Sources & evidence

ORD record
ord-3302be7dab2142ecb3d9c5d886e95b37
Source dataset
uspto-grants-2011_12
Patent number
US08076374B2

Reaction notes

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