Tetrabutylammonium Fluoride → (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-hydroxy-benzoylamino)propionic acid methyl ester

HRID 63725Notes

Reaction equation

HRID 63725 reaction equation
[CH3:1][O:2][C:3](=[O:45])[C@@H:4]([NH:23][C:24](=[O:44])[C:25]1[C:30]([Cl:31])=[CH:29][C:28]([O:32][Si](C(C)C)(C(C)C)C(C)C)=[CH:27][C:26]=1[Cl:43])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:22])[C:14]2[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:21])=[CH:8][CH:7]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:45])[C@@H:4]([NH:23][C:24](=[O:44])[C:25]1[C:26]([Cl:43])=[CH:27][C:28]([OH:32])=[CH:29][C:30]=1[Cl:31])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:22])[C:14]2[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:21])=[CH:10][CH:11]=1

Participants

6

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 89717659(S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-triisopropylsilanyloxy-benzoylamino)propionic acid methyl ester

Product 1

HCID 89719251(S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-hydroxy-benzoylamino)propionic acid methyl esterYield 99.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-triisopropylsilanyloxy-benzoylamino)propionic acid methyl ester (6.76 g, 9.48 mmol) in THF (150 mL) was added a solution of TBAF (14.22 mL, 14.22 mmol, 1M) in THF at 0° C. The resulting solution was slowly warmed to room temperature and stirred for 15 h. Then, the reaction mixture was diluted with water and the organic compound was extracted into ethyl acetate (2×150 mL). The combined organic layer was washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave the crude residue which was dissolved in ethyl acetate in hot conditions and then diluted with hexanes. The resulting solids were collected by filtration and washed with hexanes. After drying in air, 5.23 g (99%) of (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-hydroxy-benzoylamino)propionic acid methyl ester was obtained as a white solid. ES(+)-HRMS m/e calcd. for C24H18Cl4N2O5 (M−H)− 552.9897, obsd. 552.9897.

Workup

  1. extractionthe organic compound was extracted into ethyl acetate (2×150 mL)
  2. washThe combined organic layer was washed with brine solution
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationFiltration and concentration
  5. customgave the crude residue which
  6. filtrationThe resulting solids were collected by filtration
  7. washwashed with hexanes
  8. customAfter drying in air

Sources & evidence

ORD record
ord-800b0fc13add47b9b73961eb4c6fb08d
Source dataset
uspto-grants-2016_09
Patent number
US09447035B2

Reaction notes

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