Triethylamine → 2-(4-{1-Ethyl-1-[4-(1-hydroxy-cyclopentylethynyl)-3-methyl-phenyl]-propyl}-2-methyl-benzoylamino)-2-methyl-propionic acid methyl ester

HRID 736517Notes

Reaction equation

HRID 736517 reaction equation
[CH2:1]([C:3]([C:21]1[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[C:23]([CH3:30])[CH:22]=1)([C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]2([OH:19])[CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:8]([CH3:20])[CH:7]=1)[CH2:4][CH3:5])[CH3:2].Cl.[CH3:32][O:33][C:34](=[O:39])[C:35]([NH2:38])([CH3:37])[CH3:36].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>>[CH3:32][O:33][C:34](=[O:39])[C:35]([NH:38][C:25](=[O:26])[C:24]1[CH:28]=[CH:29][C:21]([C:3]([CH2:1][CH3:2])([C:6]2[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]3([OH:19])[CH2:15][CH2:16][CH2:17][CH2:18]3)=[C:8]([CH3:20])[CH:7]=2)[CH2:4][CH3:5])=[CH:22][C:23]=1[CH3:30])([CH3:37])[CH3:36]

Participants

5

Reactant 4

HCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 13258034Methyl 2-aminoisobutyrate hydrochlorideHCID 578493274-{1-Ethyl-1-[4-(1-hydroxy-cyclopentylethynyl)-3-methyl-phenyl]-propyl}-2-methyl-benzoic acid

Product 1

HCID 578493162-(4-{1-Ethyl-1-[4-(1-hydroxy-cyclopentylethynyl)-3-methyl-phenyl]-propyl}-2-methyl-benzoylamino)-2-methyl-propionic acid methyl esterYield 82.1%

Procedure

4-{1-Ethyl-1-[4-(1-hydroxy-cyclopentylethynyl)-3-methyl-phenyl]-propyl}-2-methyl-benzoic acid (389 mg, 0.962 mmol), α-aminoisobutyric acid methyl ester hydrochloride (221 mg, 1.44 mmol), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (276 mg, 1.44 mmol), 1-hydroxybenzotriazole hydrate (195 mg, 1.44 mmol) and triethylamine (536 μL, 3.85 mmol) are stirred overnight. The reaction is concentrated and partitioned between EtOAc (150 ml) and 1N HCl (50 ml). The aqueous layer is extracted with EtOAc (100 ml). The combined organic layers are washed with, water (50 ml), NaHCO3 (50 ml), brine (50 ml), dried (anhydrous MgSO4), concentrated and chromatographed (12 g SiO2, 15% EtOAc/Hexanes) to yield the title compound (398 mg, 82%).

Workup

  1. concentrationThe reaction is concentrated
  2. custompartitioned between EtOAc (150 ml) and 1N HCl (50 ml)
  3. extractionThe aqueous layer is extracted with EtOAc (100 ml)
  4. washThe combined organic layers are washed with, water (50 ml), NaHCO3 (50 ml), brine (50 ml)
  5. dry with materialdried (anhydrous MgSO4)
  6. concentrationconcentrated
  7. customchromatographed (12 g SiO2, 15% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-f2ed975c26b94a5eb73eab9045cafb2d
Source dataset
uspto-grants-2009_09
Patent number
US07595345B2

Reaction notes

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