ethyl (2R)-oxirane-2-carboxylate → 3-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenylamino]-2(R)-hydroxypropionic acid ethyl ester

HRID 723899

Reaction equation

HRID 723899 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[C:4]([F:15])[CH:3]=1.[CH2:16]([O:18][C:19]([C@H:21]1[CH2:23][O:22]1)=[O:20])[CH3:17].[O-]S(C(F)(F)F)(=O)=O.[Li+]>C(#N)C>[CH2:16]([O:18][C:19](=[O:20])[C@H:21]([OH:22])[CH2:23][NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:9]=[CH:10][C:11](=[O:14])[CH2:12][CH2:13]2)=[C:4]([F:15])[CH:3]=1)[CH3:17]

Participants

5

Reactant 3

HCID 1512667ethyl (2R)-oxirane-2-carboxylateHCID 3664839Trifluoromethanesulfonic acid, lithium saltHCID 218778771-(4-Amino-2-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

Product 1

HCID 684871023-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenylamino]-2(R)-hydroxypropionic acid ethyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 1-(4-amino-2-fluorophenyl)-2,3-dihydro-1H-pyridin-4-one (Step 4, 0.412 g, 2.0 mmol) and oxirane-2(R)-carboxylic acid ethyl ester (0.394 g, 3.4 mmol) with lithium triflate (0.360 g, 3.0 mmol) in dry acetonitrile (5.0 mL) is heated at 50–60° C. for 24 h. Volatiles are removed under vacuum, and the crude material purified by silica gel flash chromatography (eluent: 5% acetone in CH2Cl2) to afford the title compound (290 mg, 45%) as a viscous yellow oil, MS (m/z): 323 [M+H]+.

Workup

  1. customVolatiles are removed under vacuum
  2. customthe crude material purified by silica gel flash chromatography (eluent: 5% acetone in CH2Cl2)

Sources & evidence

ORD record
ord-968a0eb5cda14a0bb282c1afaddf6c99
Source dataset
uspto-grants-2006_11
Patent number
US07141588B2

Linked notes

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