4-Methoxyphenylacetic Acid → 3-(4-Cyano-3-fluoro-phenyl)-2-(4-methoxy-phenyl)-3-oxo-propionic acid methyl ester

HRID 1773363Notes

Reaction equation

HRID 1773363 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.[Li+].[CH3:14][Si]([N-][Si](C)(C)C)(C)C.[C:23]([C:25]1[CH:33]=[CH:32][C:28]([C:29](Cl)=[O:30])=[CH:27][C:26]=1[F:34])#[N:24].[NH4+].[Cl-]>C1COCC1>[CH3:14][O:11][C:10](=[O:12])[CH:9]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1)[C:29]([C:28]1[CH:32]=[CH:33][C:25]([C:23]#[N:24])=[C:26]([F:34])[CH:27]=1)=[O:30]

Participants

6

Reactant 4

HCID 76904-Methoxyphenylacetic AcidHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 199567394-Cyano-3-fluorobenzoyl chloride

Product 1

HCID 1184831003-(4-Cyano-3-fluoro-phenyl)-2-(4-methoxy-phenyl)-3-oxo-propionic acid methyl esterYield 45.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (4-methoxy-phenyl)-acetic acid (2.18 g, 12.12 mmol) in THF (20 mL) was added LiHMDS (18.2 mL, 18.18 mmol) at −78° C. and the mixture was stirred for 30 min. A solution of 4-cyano-3-fluoro-benzoyl chloride (2.2 g, 12 mmol) in THF was added dropwise at −78° C.; and the reaction mixture was allowed to warm up to RT and stirred at overnight. Aqueous NH4Cl was added and the aqueous was extracted with EA (3×). The combined organics were concentrated in vacuo and the residue was purified by silica column chrmatography (1:5, EA: PE) to give 1.8 g (45%) of the title compound. [M+H] Calc'd for C18H14FNO4, 328. Found, 328.

Workup

  1. stirringstirred at overnight
  2. extractionthe aqueous was extracted with EA (3×)
  3. concentrationThe combined organics were concentrated in vacuo
  4. customthe residue was purified by silica column chrmatography (1:5, EA: PE)

Sources & evidence

ORD record
ord-8c48481c0fc34d7c8d762b0b9912e3e6
Source dataset
uspto-grants-2016_02
Patent number
US09255097B2

Reaction notes

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