Water → 2-amino-3-methylbutyric acid 2-{[6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbonyl]-aminooxy}-ethylester

HRID 1176935Notes

Reaction equation

HRID 1176935 reaction equation
FC(F)(F)C(O)=O.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:17]([C:27]([NH:29][O:30][CH2:31][CH2:32][O:33][C:34](=[O:40])[CH:35]([NH2:39])[CH:36]([CH3:38])[CH3:37])=[O:28])=[CH:18][C:19]3[N:23]([CH3:24])[CH:22]=[N:21][C:20]=3[C:25]=2[F:26])=[C:11]([Cl:41])[CH:10]=1.C([O-])(O)=O.[Na+].O>CCOC(C)=O>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:17]([C:27]([NH:29][O:30][CH2:31][CH2:32][O:33][C:34](=[O:40])[CH:35]([NH2:39])[CH:36]([CH3:38])[CH3:37])=[O:28])=[CH:18][C:19]3[N:23]([CH3:24])[CH:22]=[N:21][C:20]=3[C:25]=2[F:26])=[C:11]([Cl:41])[CH:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 516892Sodium BicarbonateHCID 865928802-amino-3-methylbutyric acid 2-{[6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbonyl]-aminooxy}-ethylester trifluoroacetic acid salt

Product 1

HCID 724547202-amino-3-methylbutyric acid 2-{[6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbonyl]-aminooxy}-ethylesterYield 86.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-amino-3-methylbutyric acid 2-{[6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbonyl]-aminooxy}-ethylester trifluoroacetic acid salt (474 mg) was suspended in 80 mL of EtOAc. Addition of 15 mL of saturated aqueous NaHCO3 solution gave a biphasic mixture and dissolved most of the solids. Water (5 mL) was added to dissolve some turbidity seen in the aqueous layer. The layers were separated and the aqueous layer was extracted with 20 mL of EtOAc. The combined EtOAc layer was diluted with 50 mL of t-butyl methyl ether and washed with 2×25 mL of water, 10 mL of brine, dried with Na2SO4 and filtered. The organic layer was concentrated to a foam, concentrated with 2×10 mL of t-butyl methyl ether and dried under vacuum to give 340 mg (86%) of the free base as a white solid. 1H NMR (400 MHz, DMSO-d6 and D2O exchange) δ: 0.82 (d, J=6.7 Hz, 3H), 0.87 (d, J=6.7 Hz, 3H), 1.86 (m, 1H), 3.14 (d, J=5.0 Hz, 1H), 3.90 (s, 3H), 4.03 (m br, 2H), 4.24 (d br, 2H), 6.36 (dd, JH-H=8.8 Hz, JF-H=4.4 Hz virtual coupling, 1H); 7.26 (dd, J=8.8 Hz, 2.3 Hz, 1H), 7.60 (d, J=2.26 Hz, 1H), 7.75 (s, 1H), 8.40 (s, 1H), 19F NMR (376 MHz, DMSO-d6 and D2O exchange) δ: −133.03.

Workup

  1. customgave a biphasic mixture
  2. dissolutiondissolved most of the solids
  3. dissolutionto dissolve some turbidity
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with 20 mL of EtOAc
  6. additionThe combined EtOAc layer was diluted with 50 mL of t-butyl methyl ether
  7. washwashed with 2×25 mL of water, 10 mL of brine
  8. dry with materialdried with Na2SO4
  9. filtrationfiltered
  10. concentrationThe organic layer was concentrated to a foam
  11. concentrationconcentrated with 2×10 mL of t-butyl methyl ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-c3d17432de97498fb9d28258daf9c901
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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