Water → HCID 69020209, compound

HRID 1865094Notes

Reaction equation

HRID 1865094 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:16])[C:8]([CH2:14][CH3:15])=[C:9]([C:12]#[N:13])[C:10]=1I)=[O:5])[CH3:2].[F:17][C:18]1[CH:39]=[CH:38][CH:37]=[CH:36][C:19]=1[O:20][C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].O.O>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:16])[C:8]([CH2:14][CH3:15])=[C:9]([C:12]#[N:13])[C:10]=1[C:24]1[CH:23]=[CH:22][C:21]([O:20][C:19]2[CH:36]=[CH:37][CH:38]=[CH:39][C:18]=2[F:17])=[CH:26][CH:25]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 2735133Sodium Carbonate MonohydrateHCID 57975348HCID 57975348, compoundHCID 579753882-(4-(2-Fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 69020209HCID 69020209, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Combine 4-cyano-5-ethyl-3-iodo-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (prepared in preparation 38, 0.46 mmol), 2-[4-(2-fluoro-phenoxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane (1.3 Eq), tetrakis(triphenylphosphine)-palladium(0) (0.1 Eq) and 2.0 M sodium carbonate/water (6.5 Eq) in 1,4-dioxane (10 mL) and heat at −80° C. to 90° C. overnight. Let the reaction cool to room temperature and pour into water. Extract the quenched reaction mixture with ethyl acetate. Combine the organic extracts, wash with water, dry over potassium carbonate, filter, and concentrate under reduced vacuum. Purify the residue by silica gel chromatography (Chromatotron™) eluting with hexane/ethyl acetate 4:1 to provide the final title compound, 4-cyano-5-ethyl-3-[4-(2-fluoro-phenoxy)-phenyl]-1-methyl-1H-pyrole-2-carboxylic acid ethyl ester, as a tan solid. Mass spectrum (m/e): 393.1 (M*+1): (Bruker 300) 1H NMR (CDCl3) δ 7.27-7.31 (3H, d), 7.07-7.20 (3H, m), 6.95-6.99 (2H, d), 4.04-4.11 (2H, dd), 3.84-3.88 (3H, s), 2.74-2.86 (2H, dd), 1.23-1.34 (3H, t), 1.00-1.06 (3H, t).

Workup

  1. extractionExtract
  2. customthe quenched reaction mixture with ethyl acetate
  3. washwash with water
  4. dry with materialdry over potassium carbonate
  5. filtrationfilter
  6. concentrationconcentrate under reduced vacuum
  7. customPurify the residue by silica gel chromatography (Chromatotron™)
  8. washeluting with hexane/ethyl acetate 4:1

Sources & evidence

ORD record
ord-3555ca1260d744309dc89535a77d5010
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

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