Trifluoroacetic acid → 4-bromo-5-chloro-N-((2-(methylthio)benzo[d]oxazol-6-yl)methyl)-2-nitroaniline

HRID 1848228Notes

Reaction equation

HRID 1848228 reaction equation
[Br:1][C:2]1[C:8]([Cl:9])=[CH:7][C:5]([NH2:6])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.C(O)(C(F)(F)F)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:34][S:35][C:36]1[O:37][C:38]2[CH:44]=[C:43]([CH:45]=O)[CH:42]=[CH:41][C:39]=2[N:40]=1>C(Cl)Cl>[Br:1][C:2]1[C:8]([Cl:9])=[CH:7][C:5]([NH:6][CH2:45][C:43]2[CH:42]=[CH:41][C:39]3[N:40]=[C:36]([S:35][CH3:34])[O:37][C:38]=3[CH:44]=2)=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 218469994-Bromo-5-chloro-2-nitroanilineHCID 866811372-(Methylthio)benzo[d]oxazole-6-carboxaldehyde

Product 1

HCID 866812004-bromo-5-chloro-N-((2-(methylthio)benzo[d]oxazol-6-yl)methyl)-2-nitroanilineYield 48.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 4-bromo-5-chloro-2-nitroaniline (550 mg, 2.19 mmol) from the previous step and TFA (2.26 mL) in DCM (10 mL) at −15° C. was added NaBH(OAc)3 (1.39 g, 5.37 mmol). Then a solution of 2-(methylthio)benzo[d]oxazole-6-carbaldehyde (465 mg, 2.41 mmol) in DCM (6 mL) was added to the mixture. After complete addition, the mixture was stirred at −10° C. to 0° C. for 2 h. The reaction mixture was diluted with DCM and washed sequentially with H2O, aq NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 5:1 to 2:1 petroleum ether/DCM to give 4-bromo-5-chloro-N-((2-(methylthio)benzo[d]oxazol-6-yl)methyl)-2-nitroaniline as a yellow solid (451 mg, 48.2%). 1H NMR (300 MHz, DMSO-d6) δ 8.81 (t, 1H), 8.34 (s, 1H), 7.66 (s, 1H), 7.60 (d, J=8.1 Hz, 1H), 7.37 (d, J=6.9 Hz, 1H), 7.19 (s, 1H), 4.76 (d, J=6.3 Hz, 2H), 2.74 (s, 3H). LCMS (ESI) m/z 428 (M+H)+.

Workup

  1. additionAfter complete addition
  2. washwashed sequentially with H2O, aq NaHCO3 and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 5:1 to 2:1 petroleum ether/DCM

Sources & evidence

ORD record
ord-7450e5e5638744aeb978a917ec744884
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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