Triphenylphosphine → (R)-2-(4-Cyano-3-fluoro-phenoxy)-propionic Acid Methyl Ester

HRID 350977Notes

Reaction equation

HRID 350977 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[C:11]([O:16][CH3:17])(=[O:15])[C@H:12]([CH3:14])O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(OCC)(=O)C>[CH3:17][O:16][C:11](=[O:15])[C@H:12]([O:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=1)[CH3:14]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 94386methyl (S)-lactateHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 27346752-Fluoro-4-hydroxybenzonitrile

Product 1

HCID 60128060(R)-2-(4-Cyano-3-fluoro-phenoxy)-propionic Acid Methyl EsterYield 36%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-fluoro-4-hydroxybenzonitrile (0.2 g, 1.5 mmol), methyl (S)-(−)-lactate (0.14 mL, 1.5 mmol) and triphenylphosphine (1.15 g, 4.4 mmol) at room temperature, diethyl azodicarboxylate (0.67 mL, 4.4 mmol) was added dropwise. The mixture was stirred at room temperature overnight, diluted with ethyl acetate and washed successively with dilute aqueous sodium hydroxide, dilute aqueous hydrochloric acid, brine, and dried (Na2SO4). Solvents were stripped in vacuo. The resulting oil was washed with diethyl ether and the precipitate was filtered off. The mother liquor was adsorbed onto silica gel and the product purified by flash column chromatography (20% dichloromethane/hexane), affording 0.12 g of a pink oil (36% yield).

Workup

  1. washwashed successively with dilute aqueous sodium hydroxide, dilute aqueous hydrochloric acid, brine
  2. dry with materialdried (Na2SO4)
  3. washThe resulting oil was washed with diethyl ether
  4. filtrationthe precipitate was filtered off
  5. customthe product purified by flash column chromatography (20% dichloromethane/hexane)

Sources & evidence

ORD record
ord-120dcfea887341f5bb3b2eba2221a15e
Source dataset
uspto-grants-2007_02
Patent number
US07183293B2

Reaction notes

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