反应详情

温度

-78 °C

In a 4 L mechanically stirred reactor, a solution of 1-benzothien-7-yl methyl ether (105 g, 0.64 mol) in anhydrous THF (2 L) is cooled down to −74° C. n-Butyl lithium in hexane is added (2.5 N, 285 mL, 0.71 mol) within 45 min, keeping temperature below −70° C. The mixture is stirred 30 min at −78° C. and a solution of iodine (179 g, 0.70 mol) in anhydrous THF (1 L) is added within 1 h, keeping temperature below −70° C. After addition, the mixture is allowed to come up to room temperature over 2 h and brine (500 mL) is added. The layers are roughly separated and the organic layer is partially evaporated. Additional brine (200 mL) is added to the residual aqueous layer (mixed with some THF). After decantation, the organic and aqueous layers are separated. The aqueous layer is extracted with ethyl acetate (500 mL). The organic layers are pooled, washed with aqueous sodium thiosulphate, dried (MgSO4) and the solvent evaporated in vacuo to give the crude iodo derivative (173.6 g, 93%) The solid is recrystallized from isopropanol (150 mL) to give pure compound (145.5 g, 88%); δH (600 MHz, CDCl3) 7.51 (s, 1H), 7.32 (d(br), J=7.89 Hz, 1H), 7.26 (t, J=7.89 Hz, 1H), 6.72 (d(br), J=7.89 Hz, 1H), 3.97 (s, 3H).

1. additionis added (2.5 N, 285 mL, 0.71 mol) within 45 min
2. customtemperature below −70° C
3. customtemperature below −70° C
4. additionAfter addition
5. waitto come up to room temperature over 2 h
6. customThe layers are roughly separated
7. customthe organic layer is partially evaporated
8. additionAdditional brine (200 mL) is added to the residual aqueous layer (
9. additionmixed with some THF)
10. customAfter decantation, the organic and aqueous layers are separated
11. extractionThe aqueous layer is extracted with ethyl acetate (500 mL)
12. washwashed with aqueous sodium thiosulphate
13. dry with materialdried (MgSO4)
14. customthe solvent evaporated in vacuo
15. customto give the crude iodo derivative (173.6 g, 93%) The solid
16. customis recrystallized from isopropanol (150 mL)