Methyl 3-[2-benzyloxy-5-(2-chloroethyl)-4-nitroanilino]-4,4,4-trifluoro-2-butenoate → Methyl 7-benzyloxy-4-(2-cloroethyl)-5-nitro-2-trifluoromethylindole-3-carboxylate

HRID 431726Notes

Reaction equation

HRID 431726 reaction equation
[CH2:1]([O:8][C:9]1[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[C:23]([CH2:29][CH2:30][Cl:31])=[CH:22][C:10]=1[NH:11][C:12]([C:18]([F:21])([F:20])[F:19])=[CH:13][C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CC(O)=O.CC(O)=O.[Pd]>[CH2:1]([O:8][C:9]1[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[C:23]([CH2:29][CH2:30][Cl:31])=[C:22]2[C:10]=1[NH:11][C:12]([C:18]([F:19])([F:20])[F:21])=[C:13]2[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 69546885Methyl 3-[2-benzyloxy-5-(2-chloroethyl)-4-nitroanilino]-4,4,4-trifluoro-2-butenoate

Product 1

HCID 18761439Methyl 7-benzyloxy-4-(2-cloroethyl)-5-nitro-2-trifluoromethylindole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 4144353Palladium (II) acetateCatalyst

Conditions

Temperature
68 °C

Procedure

Methyl 3-[2-benzyloxy-5-(2-chloroethyl)-4-nitroanilino]4,4,4-trifluoro-2-butenoate (0.035 g, 0.0763 mmol) was dried under high vacuum in a round bottom flask. Palladium II acetate (0.034 g, 0.153 mmol) was added, the flask was then covered with a septum and flushed with N2. Dry dimethyl acetamiide (20 mL) was then added via syringe under N2. The solution was then degassed three times under vacuum for thirty minutes and purged with N2. The solution was then stirred for six hours and fifteen minutes in an oil bath at 68° C. The solution was then diluted with CHCl3 (100 mL) and washed with water three times (100 mL). The organic layer was dried with sodium sulfate, gravity filtered and concentrated on rotovap. The dimethylacetamide was removed under high vacuum Kugelrohr distillation (50° C., 0.25 mm Hg). The residue was purified on silica gel column using methylene chloride as a solvent to yield methyl 7-benzyloxy-4-(2-cloroethyl)-5-nitro-2-trifluoromethylindole-3-carboxylate as a yellow solid. Total yield: 0.010 g (0.022 mmol, 29%). TLC (methylene chloride) Rf320.75.500 MHz 1H-NMR (CDCl3) 9.24 (s br, 1H), 7.46 (m, 5H), 7.44 (s, 1H), 5.26 (s, 2H), 4.01 (s, 3H), 3.82 (t, 7.5, 2H), 3.63 (t, 7.5, 2H). IR (neat) 3036, 2952, 2915, 2850, 1732, 1713, 1695, 1576, 1534, 1503, 1451, 1337, 1259, 865, 802. EI-MS (relative intensity) 456 (M+, 3), 420 (M+−HCl, 3). Accurate mass for C20H16O9N235ClF3: calcd. 456.0700, obsd. 456.0695.

Workup

  1. customflushed with N2
  2. additionDry dimethyl acetamiide (20 mL) was then added via syringe under N2
  3. customThe solution was then degassed three times under vacuum for thirty minutes
  4. custompurged with N2
  5. additionThe solution was then diluted with CHCl3 (100 mL)
  6. washwashed with water three times (100 mL)
  7. dry with materialThe organic layer was dried with sodium sulfate, gravity
  8. filtrationfiltered
  9. concentrationconcentrated on rotovap
  10. customThe dimethylacetamide was removed under high vacuum Kugelrohr distillation (50° C., 0.25 mm Hg)
  11. customThe residue was purified on silica gel column

Sources & evidence

ORD record
ord-648defbf4ba8432d8774b3e94a75a186
Source dataset
uspto-grants-2003_12
Patent number
US06660742B2

Reaction notes

Loading…