تفاعل #496217

معادلة التفاعل

NCS

Triphenylphosphine

(5S,6S,9R)-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-ol

→

desired product

المردود 83.0%

(5R,6S,9R)-5-chloro-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine

المردود 83.0%

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىIn an oven-dried 250 mL round-bottom flask was suspended
2. 2
   workup.STIRRINGThe resulting reddish suspension was stirred at room temperature
3. 3
   workup.DISSOLUTIONThe solids gradually dissolved
4. 4
   أخرىto give a tan solution
5. 5
   workup.WAITAfter 5 h
6. 6
   أخرىTetrahydrofuran was removed in vacuo
7. 7
   أخرىthe remaining red oil was directly purified by ISCO (240 g silica column) up to 60% ethyl acetate/hexane
8. 8
   غسيلPure ethyl acetate eluted the non polar component
9. 9
   غسيلthe product was eluted by 10% methanol (with 2.0M NH4OH) in methylene chloride
10. 10
    أخرىre-purified by FCC up to 50% ethyl acetate/hexane

الإجراء التجريبي

In an oven-dried 250 mL round-bottom flask was suspended NCS (0.751 g, 5.62 mmol) in tetrahydrofuran (15 mL). Triphenylphosphine (1.475 g, 5.62 mmol) was added. After stirring under nitrogen for 5 min, (5S,6S,9R)-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-ol (1.007 g, 2.250 mmol) was added in one portion to the gray suspension. The resulting reddish suspension was stirred at room temperature. The solids gradually dissolved to give a tan solution. After 5 h, LCMS indicated complete conversion. Tetrahydrofuran was removed in vacuo and the remaining red oil was directly purified by ISCO (240 g silica column) up to 60% ethyl acetate/hexane. Pure ethyl acetate eluted the non polar component and the product was eluted by 10% methanol (with 2.0M NH4OH) in methylene chloride. The product fractions were combined and re-purified by FCC up to 50% ethyl acetate/hexane to afford the desired product as a colorless oil (869 mg, 83%). MS (ESI) [M+H+]=466.22; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.55 (d, J=3.53 Hz, 1H) 7.63 (br. s., 1H) 7.20 (dd, J=7.68, 4.91 Hz, 1H) 7.01-7.15 (m, 1H) 6.90-7.01 (m, 1H) 6.66-6.90 (m, 1H) 5.55-5.85 (m, 1H) 5.40-5.56 (m, 1H) 3.96-4.33 (m, 1H) 2.33 (br. s., 3H) 2.09-2.20 (m, 1H) 1.14-1.23 (m, 3H) 1.04-1.14 (m, 9H) 1.01 (d, J=7.30 Hz, 9H).

المصدر