N-bromobutanimide → Ethyl 2-(2-bromothiophen-3-yl)acetate

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.

1. customThe solvent was removed in vacuo
2. dissolutionthe residue as dissolved in EtOAc (150 mL)
3. washwashed with brine (4×30 mL)
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customMPLC purification (Hex:EtOAc/5:1) of the residue

ORD record

ord-7a6c4d97dbd84e2ebf2d8367f7faef04

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404728B2