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

HRID 1058400Notes

Reaction equation

HRID 1058400 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.C(N(CC)CC)C.[C]=O.[C:44]([O:47]CC)(=[O:46])C>C(#N)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[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:44]([OH:47])=[O:46]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 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 4

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 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]benzyl]amino]carbonyl]phenyl ester (Example 105, 562 mg, 1.09 mmol) in acetonitrile (7 mL) and water (1 mL) at 25° C. was added palladium (II) acetate (24 mg, 0.109 mmol), 1,3-bis(diphenylphosphino)propane (45 mg, 0.109 mmol), followed by triethylamine (2.18 mmol, 0.303 mL). 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 (100 mL) and washed with water (50 mL) containing 1 mL of triethylamine. The separated aqueous layer was re-extracted with ethyl acetate (2×50 mL) and the combined organic layers were discarded. The aqueous phase was adjusted with 1N hydrochloric acid solution to pH 2 and extracted with ethyl acetate (100 mL). The organic extract was washed with water (25 mL) and brine (25 mL), dried (MgSO4), filtered and evaporated under reduced pressure to yield 2,6-dimethyl-4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]benzoic acid (1.7 g, 71% yield) as a colorless solid.

Workup

  1. washwashed with water (50 mL)
  2. additioncontaining 1 mL of triethylamine
  3. extractionThe separated aqueous layer was re-extracted with ethyl acetate (2×50 mL)
  4. extractionextracted with ethyl acetate (100 mL)
  5. extractionThe organic extract
  6. washwas washed with water (25 mL) and brine (25 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-84a201c0b3504294b46a57c0d54e0180
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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