Hydrochloric Acid → 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)benzo[d]oxazole-6-carboxamide

HRID 928973Notes

Reaction equation

HRID 928973 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][CH2:24][O:25]C=C)=[O:20])=[CH:11][C:12]3[O:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:28])[CH:3]=1.Cl>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][CH2:24][OH:25])=[O:20])=[CH:11][C:12]3[O:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:28])[CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 897048595-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-(vinyl-oxy)ethoxy)benzo[d]oxazole-6-carboxamide

Product 1

HCID 716676615-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)benzo[d]oxazole-6-carboxamideYield 82.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-(vinyloxy)ethoxy)benzo[d]oxazole-6-carboxamide (445 mg, 0.95 mmol) in CH2Cl2 (10 mL) was added 1.0 N HCl solution (6.7 mL, 6.72 mmol). After stirring for 1 h, the reaction mixture was washed with saturated NaHCO3 (aq.). The aqueous layer was extracted with CH2Cl2 (10 mL×2). The combined organic layer was washed with water (10 mL) and brine (10 mL) successively, 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) and gave the desired product (white solid, 347 mg, 65% yield for two steps). 1H NMR (400 MHz, MeOD): δ 8.65 (s, 1H), 7.8 (s, 1H), 7.54 (d, J=2.0 Hz, 1H), 7.24 (m, 1H), 6.50 (m, 1H), 3.95 (s, 2H), 3.70 (s, 2H). MS APCI (+) m/z: 445.9[M+H], 467.8, [M+Na].

Workup

  1. washthe reaction mixture was washed with saturated NaHCO3 (aq.)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (10 mL×2)
  3. washThe combined organic layer was washed with water (10 mL) and brine (10 mL) successively
  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-ba3be0e6f6ab4316962e1a55fc7e5975
Source dataset
uspto-grants-2016_03
Patent number
US09290468B2

Reaction notes

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