4-Benzyloxy-2-nitroaniline → 4-(benzyloxy)-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline

HRID 1848159Notes

Reaction equation

HRID 1848159 reaction equation
[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[C:11]([N+:16]([O-:18])=[O:17])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:33][S:34][C:35]1[S:36][C:37]2[CH:43]=[C:42]([CH:44]=O)[CH:41]=[CH:40][C:38]=2[N:39]=1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:12]([NH:13][CH2:44][C:42]2[CH:41]=[CH:40][C:38]3[N:39]=[C:35]([S:34][CH3:33])[S:36][C:37]=3[CH:43]=2)=[C:11]([N+:16]([O-:18])=[O:17])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 2614974-Benzyloxy-2-nitroanilineHCID 5049666Sodium triacetoxyborohydrideHCID 547753816-Benzothiazolecarboxaldehyde, 2-(methylthio)-

Product 1

HCID 866811284-(benzyloxy)-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroanilineYield 64.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of 4-(benzyloxy)-2-nitroaniline (2.0 g, 8.2 mmol) in TFA (14 mL) at −15° C. was added sodium triacetoxyborohydride (2.84 g, 12 mmol). Then a solution of 2-(methylthio)benzo[d]thiazole-6-carbaldehyde (1.9 g, 9.0 mmol) from Step 1 of Example 100 in DCM (10 mL) was added dropwise. The reaction mixture was allowed to warm to 0° C. and stir for 2 h. The mixture was partitioned between DCM and water. The organic layer was separated and washed sequentially with saturated aq NaHCO3 and brine. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with a gradient of 10% EtOAc in petroleum ether to 100% EtOAc to afford 4-(benzyloxy)-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline (2.3 g, 64%) as a red-brown solid. 1H NMR (300 MHz, CDCl3) δ 8.34 (s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.72-7.77 (m, 2H), 7.33-7.43 (m, 6H), 7.14 (m, 1H), 6.76 (d, J=9.6 Hz, 1H), 5.02 (s, 2H), 4.64 (d, J=5.7 Hz, 2H), 2.79 (s, 3H); LCMS (ESI) m/z 438 (M+H)+.

Workup

  1. customThe mixture was partitioned between DCM and water
  2. customThe organic layer was separated
  3. washwashed sequentially with saturated aq NaHCO3 and brine
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography
  9. washeluting with a gradient of 10% EtOAc in petroleum ether to 100% EtOAc

Sources & evidence

ORD record
ord-d85169c2270e4ca79bcdc6fe7db29415
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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