تفاعل #1557605

معادلة التفاعل

iodomethane

tert-butyl 2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-ylcarbamate

sodium hydride

→

tert-butyl 2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-yl(methyl)carbamate

المردود 91.1%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe reaction mixture was stirred at 0° C. for 30 min
2. 2
   أخرىThe ice-water bath was removed
3. 3
   workup.STIRRINGthe mixture was stirred for an additional 1 hour
4. 4
   workup.ADDITIONdiluted with ethyl acetate (100 mL) and aqueous sodium bicarbonate (5 mL)
5. 5
   أخرىThe organic phase was separated
6. 6
   غسيلrinsed with brine
7. 7
   تجفيفdried over MgSO4
8. 8
   ترشيحfiltered
9. 9
   تركيزconcentrated in vacuo
10. 10
    أخرىto give a yellow residue
11. 11
    أخرىThis residue was purified on silica gel chromatography (6:4 hexane/ethyl acetate)

الإجراء التجريبي

To a solution of tert-butyl 2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-ylcarbamate (1.20 g, 2.85 mmol) in DMF (5.7 mL) at 0° C. was added sodium hydride (125 mg, 3.13 mmol, 60% oil suspension) and the mixture was stirred at 0° C. for 10 min. To the yellow mixture was added iodomethane (0.49 g, 3.42 mmol) and the reaction mixture was stirred at 0° C. for 30 min. The ice-water bath was removed and the mixture was stirred for an additional 1 hour. The mixture was acidified with 0.1 N aq. HCl to neutral pH and diluted with ethyl acetate (100 mL) and aqueous sodium bicarbonate (5 mL). The organic phase was separated and rinsed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a yellow residue. This residue was purified on silica gel chromatography (6:4 hexane/ethyl acetate) to give tert-butyl 2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-yl(methyl)carbamate as a pale yellow solid (1.13 g, 91%): mp 70-71° C.; 1H NMR (300 MHz, CDCl3) δ 8.87 (s, 1H), 8.53 (bs, 1H), 7.99 (d, J=0.9 Hz, 1H), 3.23 (s, 3H), 1.45 (s, 9H); ESIMS m/z 436.1 (M+1).

المصدر