Ammonium Chloride → 3-(3-Fluoro-4-hydroxy-benzoylamino)-propionic acid ethyl ester

HRID 1669334Notes

Reaction equation

HRID 1669334 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[OH:11])[C:5]([OH:7])=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.[CH2:46]([O:48][C:49](=[O:53])[CH2:50][CH2:51][NH2:52])[CH3:47].C(N(C(C)C)C(C)C)C.[Cl-].[NH4+]>CN(C)C=O.O.C(OCC)(=O)C>[CH2:46]([O:48][C:49](=[O:53])[CH2:50][CH2:51][NH:52][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][C:10]([OH:11])=[C:2]([F:1])[CH:3]=1)[CH3:47]

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 1604563-Fluoro-4-hydroxybenzoic acidHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 2724699PyBOP

Product 1

HCID 597294013-(3-Fluoro-4-hydroxy-benzoylamino)-propionic acid ethyl esterYield 76%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 3-Fluoro-4-hydroxy-benzoic acid (1.0 g, 6.4 mmol), PyBOP (4.0 g, 7.69 mmol), 3-amino-propionic acid ethyl ester hydrochloride (1.47 g, 9.6 mmol) and ethyl-diisopropyl-amine (4.55 mL, 25.6 mmol) in N,N-dimethyl-formamide (20 mL). Stir for sixty-six hours at room temperature. Dilute reaction with ethyl acetate and water. Wash organic layer with saturated solution of ammonium chloride and water. Extract combined aqueous fraction with ethyl acetate. Wash combined organic fractions with saturated sodium chloride solution. Dry organic fraction with Na2SO4, filter and concentrate under reduced pressure. Purify on silica gel chromatography (20-80% Ethyl acetate/hexanes gradient) to provide 1.24 g of title compound (76%).

Workup

  1. additionDilute
  2. extractionExtract
  3. washWash
  4. filtrationDry organic fraction with Na2SO4, filter
  5. concentrationconcentrate under reduced pressure
  6. customPurify on silica gel chromatography (20-80% Ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-da6e89c6f11a4f149c0594ef2e52116e
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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