Aluminum(III) Chloride → Ethyl 2-(2-bromo-5-(4-iodo-3-nitrobenzoyl)thiophen-3-yl)acetate

HRID 1952505Notes

Reaction equation

HRID 1952505 reaction equation
[Br:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[I:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][C:15]=1[N+:23]([O-:25])=[O:24].[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl>[Br:1][C:2]1[S:3][C:4]([C:18](=[O:19])[C:17]2[CH:21]=[CH:22][C:14]([I:13])=[C:15]([N+:23]([O-:25])=[O:24])[CH:16]=2)=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

5

Reactant 3

HCID 6451240Aluminum(III) ChlorideHCID 589329354-Iodo-3-nitrobenzoyl chlorideHCID 67496474Ethyl 2-(2-bromothiophen-3-yl)acetate

Product 1

HCID 67495826Ethyl 2-(2-bromo-5-(4-iodo-3-nitrobenzoyl)thiophen-3-yl)acetateYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl 2-(thiophen-3-yl)acetate (20.30 g, 119.25 mmol) in THF (150 mL) was added NBS (21.23 g, 119.25 mmol) during a period of 5 hours at 0° C., and then the mixture was warmed up to room temperature, stirring continuously for 24 hours. The solvent was removed in vacuo, and then the residue as dissolved in EtOAc (150 mL) and washed with brine (4×30 mL). The organic layer was dried over MgSO4, filtered, and then concentrated in vacuo. MPLC purification (Hex:EtOAc/5:1) of the residue gave ethyl 2-(2-bromothiophen-3-yl)acetate as a colorless oil (24.00 g, 81%). 1H NMR (400 MHz, CDCl3) δ 7.23 (d, J=5.4 Hz, 1H), 6.93 (d, J=5.4 Hz, 1H), 4.17 (q, J=7.2 Hz, 2H), 3.61 (s, 2H), and 1.27 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.37, 133.84, 128.90, 125.93, 111.78, 61.32, 35.30, and 14.43. To a solution of ethyl 2-(2-bromothiophen-3-yl)acetate (24.00 g, 96.32 mmol) and 4-iodo-3-nitrobenzoyl chloride (30.00 g, 96.32 mmol) in anhydrous CH2Cl2 (100 mL) was added AlCl3 (38.53 g, 288.96 mmol) over a period of 4 hours at room temperature. The resulting mixture was stirred for 2 days. The reaction mixture was slowly poured onto 200 g of ice and allowed to warm to room temperature. The aqueous phase was extracted with Et2O (4×30 mL), and the combined organic layer was dried over MgSO4, filtered, and then concentrated in vacuo. MPLC purification of (Hex:EtOAc/4:1) of the residue gave 2 as a light yellow solid (20.00 g, 40%). 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J=2.0 Hz, 1H), 8.21 (d, J=8.2 Hz, 1H), 7.69 (dd, J=2.0, 8.2 Hz, 1H), 7.48 (s, 1H), 4.19 (q, J=7.2 Hz, 2H), 3.66 (s, 2H), and 1.28 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 183.84, 169.61, 153.25, 142.83, 141.87, 138.32, 136.49, 135.94, 133.07, 125.69, 124.50, 91.79, 61.76, 35.20, and 14.42.

Workup

  1. extractionThe aqueous phase was extracted with Et2O (4×30 mL)
  2. dry with materialthe combined organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customMPLC purification of (Hex:EtOAc/4:1) of the residue

Sources & evidence

ORD record
ord-6828a33fee924254b360531de921c9e0
Source dataset
uspto-grants-2013_03
Patent number
US08404728B2

Reaction notes

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