Triethylamine → 2,6-Dimethyl-4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]benzoic acid

HRID 1726734Notes

Reaction equation

HRID 1726734 reaction equation
FC(F)(F)S(O[C:7]1[C:12]([CH3:13])=[CH:11][C:10]([C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH:19]=2)=[O:15])=[CH:9][C:8]=1[CH3:32])(=O)=O.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[C]=O.[C:73]([O:76]CC)(=[O:75])C>C(#N)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:13][C:12]1[CH:11]=[C:10]([C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][Si:25]([C:28]([CH3:31])([CH3:29])[CH3:30])([CH3:26])[CH3:27])[CH:19]=2)=[O:15])[CH:9]=[C:8]([CH3:32])[C:7]=1[C:73]([OH:76])=[O:75]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 23560804Trifluoromethanesulfonic acid, 2,6-dimethyl-4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]phenyl esterHCID 178418416HCID 178418416, compound

Product 1

HCID 226615542,6-Dimethyl-4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]benzoic acidYield 71%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of trifluoromethanesulfonic acid, 2,6-dimethyl-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]phenyl ester (Example 23; 3.02 g, 5.83 mmol) in acetonitrile (49 mL) and water (7 mL) at 25° C. was added palladium(II) acetate (196 mg, 0.874 mmol), 1,3-bis(diphenylphosphino)propane (360 mg, 0.873 mmol), followed by triethylamine (2.03 mL, 14.5 mmol). The reaction was then pressurized to 40 psi with carbon monoxide and heated to 80° C. for 4 h. The mixture was diluted with ethyl acetate (300 mL) and washed with water (100 mL) containing 1 mL of triethylamine. The water layer was reextracted with ethyl acetate (2×50 mL) and the combined ethyl acetate layers were discarded. The water layer was acidified with 1 N HCl to pH 2, and extracted with ethyl acetate (200 mL). The ethyl acetate layer was washed with water (50 mL) and brine (50 mL), dried (MgSO4), filtered and concentrated to yield 2,6-dimethyl-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]benzoic acid (1.7 g, 71%) as a white solid.

Workup

  1. washwashed with water (100 mL)
  2. additioncontaining 1 mL of triethylamine
  3. extractionextracted with ethyl acetate (200 mL)
  4. washThe ethyl acetate layer was washed with water (50 mL) and brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4bc259ee6e7148888094f0b0357811d2
Source dataset
uspto-grants-2009_02
Patent number
US07491741B2

Reaction notes

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