Trifluoroacetic acid → 5-((4-bromo-2-chlorophenyl)amino)-N-(2,3-dihydroxypropoxy)-4-fluorobenzo[d]oxazole-6-carboxamide

HRID 928975Notes

Reaction equation

HRID 928975 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19]([NH:21][O:22][CH2:23][CH:24]3[CH2:28][O:27]C(C)(C)[O:25]3)=[O:20])=[CH:11][C:12]3[O:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:31])[CH:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19]([NH:21][O:22][CH2:23][CH:24]([OH:25])[CH2:28][OH:27])=[O:20])=[CH:11][C:12]3[O:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:31])[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 897050365-((4-bromo-2-chlorophenyl)amino)-N-((2,2-dimethyl-1, 3-dioxolan-4-yl)methoxy)-4-fluorobenzo[d]oxazole-6-carboxamide

Product 1

HCID 716676625-((4-bromo-2-chlorophenyl)amino)-N-(2,3-dihydroxypropoxy)-4-fluorobenzo[d]oxazole-6-carboxamideYield 58.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-((4-bromo-2-chlorophenyl)amino)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-4-fluorobenzo[d]oxazole-6-carboxamide (473 mg, 0.92 mmol) in CH2Cl2 (10 mL) was added trifluoroacetic acid (0.2 mL, 2.69 mmol). The mixture was stirred for 1 h and washed with saturated sodium bicarbonate (aq.). The aqueous layer was extracted by CH2Cl2 (10 mL×2). The combined organic layers were washed by water (10 mL) and brine (10 mL) sequentially, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (CH2Cl2/MeOH, 50:1, v/v) to afford the desired product (white solid, 255 mg, 44.7% yield for two steps). 1H NMR (400 MHz, DMSO-d6): δ 11.78 (s, 1H), 8.95 (s, 1H), 8.05 (s, 1H), 7.89 (s, 1H), 7.54 (d, 1H), 7.30 (d, 1H), 6.42 (m, 1H), 4.83 (d, 1H), 4.62 (m, 1H), 3.86 (m, 1H), 3.70 (m, 2H), 3.35 (m, 2H). MS APCI (+) m/z: 475.7, [M+H].

Workup

  1. washwashed with saturated sodium bicarbonate (aq.)
  2. extractionThe aqueous layer was extracted by CH2Cl2 (10 mL×2)
  3. washThe combined organic layers were washed by water (10 mL) and brine (10 mL) sequentially
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography on silica gel (CH2Cl2/MeOH, 50:1

Sources & evidence

ORD record
ord-2ce3f97338f24a6abca2061aea8fcdd8
Source dataset
uspto-grants-2016_03
Patent number
US09290468B2

Reaction notes

Loading…