Hydrochloric Acid → (S)-2-(4-isobutyl-phenyl)-propionic acid 2-(3,5-dichloro-pyridin-4-yl)-1-(3,4-dimethoxy-phenyl)-ethyl ester

HRID 2076272Notes

Reaction equation

HRID 2076272 reaction equation
Cl.C(N=C=NCCCN(C)C)C.Cl.[Cl:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([Cl:34])[C:20]=1[CH2:21][CH:22]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=1)[OH:23].[CH2:35]([C:39]1[CH:44]=[CH:43][C:42]([C@H:45]([CH3:49])[C:46](O)=[O:47])=[CH:41][CH:40]=1)[CH:36]([CH3:38])[CH3:37].[NH4+].[Cl-]>CN(C)C1C=CN=CC=1.C(Cl)Cl.C(Cl)CCl>[Cl:34][C:19]1[CH:18]=[N:17][CH:16]=[C:15]([Cl:14])[C:20]=1[CH2:21][CH:22]([O:23][C:46](=[O:47])[C@H:45]([C:42]1[CH:43]=[CH:44][C:39]([CH2:35][CH:36]([CH3:38])[CH3:37])=[CH:40][CH:41]=1)[CH3:49])[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 39912DexibuprofenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 670959732-(3,5-Dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethanol

Product 1

HCID 67096033(S)-2-(4-isobutyl-phenyl)-propionic acid 2-(3,5-dichloro-pyridin-4-yl)-1-(3,4-dimethoxy-phenyl)-ethyl esterYield 82.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

(1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride) (EDC. HCl) (345 mg, 3 eq.) is added to a solution of 2-(3,5-dichloro-pyridin-4-yl)-1-(3,4-dimethoxy-phenyl)-ethanol (200 mg, 1 eq.), (S)-2-(4-isobutyl-phenyl)-propionic acid (148 mg, 1.2 eq.) and 4-dimethylaminopyridine (DMAP) (37 mg, 0.5 eq.) in dry CH2Cl2 (8 mL) at room temperature under nitrogen atmosphere. The mixture is stirred at room temperature overnight, then it is treated with a saturated solution of NH4Cl (20 ml) and extracted with EtOAc (2×20 ml). The combined organic layer are dried over Na2SO4 and the solvent is evaporated. The crude is purified by flash chromatography on silica gel in gradient elution (from petroleum ether/EtOAc 9/1 v/v to petroleum ether/EtOAc 7/3 v/v) to yield 259 mg of pure compound.

Workup

  1. extractionextracted with EtOAc (2×20 ml)
  2. dry with materialThe combined organic layer are dried over Na2SO4
  3. customthe solvent is evaporated
  4. customThe crude is purified by flash chromatography on silica gel in gradient elution (from petroleum ether/EtOAc 9/1 v/v to petroleum ether/EtOAc 7/3 v/v)

Sources & evidence

ORD record
ord-e390d32bd2704de28cd8fbf9d76eb674
Source dataset
uspto-grants-2011_04
Patent number
US07923565B2

Reaction notes

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