Potassium Carbonate → (S)-4-(2-tert-Butoxycarbonylamino-2-methoxycarbonylethyl)-3,5-dimethylbenzoic acid

HRID 1620134Notes

Reaction equation

HRID 1620134 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9](S(C(F)(F)F)(=O)=O)=[CH:8][C:7]=1[CH3:20].[C:30]([O-])([O-:32])=[O:31].[K+].[K+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:25]([O:24][C:22]([NH:21][C@H:4]([C:3]([O:2][CH3:1])=[O:29])[CH2:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([C:30]([OH:32])=[O:31])=[CH:8][C:7]=1[CH3:20])=[O:23])([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 66893221(S)-2-tert-butoxycarbonylamino-3-(2,6-dimethyl-4-trifluoromethanesulfonylphenyl)-propionic acid methyl ester

Product 1

HCID 58631279(S)-4-(2-tert-Butoxycarbonylamino-2-methoxycarbonylethyl)-3,5-dimethylbenzoic acidYield 94.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of (S)-2-tert-butoxycarbonylamino-3-(2,6-dimethyl-4-trifluoromethanesulfonylphenyl)-propionic acid methyl ester (9.68 g, 21.3 mmol), K2CO3 (14.1 g, 0.102 mol), Pd(OAc)2 (0.48 g, 2.13 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (2.56 g, 4.47 mmol) in DMF (48 mL) was bubbled in gaseous CO for 15 min. The mixture was heated to 60° C. for 8 h with a CO balloon. The cool mixture was partitioned between NaHCO3 and EtOAc, and filtered. The aqueous layer was separated, acidified with 10% citric acid aqueous solution, extracted with EtOAc, and finally dried over Na2SO4. Filtration and concentration of the filtrate resulted in a residue. The residue was recrystallized from EtOAc-hexanes to afford the desired product (7.05 g, 94%); 1H NMR (300 MHz, CDCl3): δ 1.36 (9H, s), 2.42 (6H, s), 3.14 (2H, J=7.4 Hz), 3.65 (3H, s), 4.57-4.59 (1H, m), 5.14 (1H, d, J=8.6 Hz), 7.75 (2H, s); MS (ES+) (relative intensity): 251.9 (100) (M-Boc)+.

Workup

  1. customwas bubbled in gaseous CO for 15 min
  2. customThe cool mixture was partitioned between NaHCO3 and EtOAc
  3. filtrationfiltered
  4. customThe aqueous layer was separated
  5. extractionextracted with EtOAc
  6. dry with materialfinally dried over Na2SO4
  7. filtrationFiltration and concentration of the filtrate
  8. customresulted in a residue
  9. customThe residue was recrystallized from EtOAc-hexanes

Sources & evidence

ORD record
ord-fb0e31157d8e4ee0a523f58057ab6994
Source dataset
uspto-grants-2014_07
Patent number
US08772325B2

Reaction notes

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