تفاعل #160494

معادلة التفاعل

diiodomethane

diethylzinc

(E)-3-(4-bromophenyl)prop-2-en-1-ol

DME

→

title compound

(1S,2S)-[2-(4-Bromophenyl)cyclopropyl]methanol

المذيبات

DCM

DCM

DCM

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe temperature was maintained from −5° to −10° C. throughout the additions
2. 2
   أخرىIt was quenched with saturated aqueous NH4Cl (300 mL), HCl (1N, 480 mL)
3. 3
   workup.ADDITIONdiluted with ether (900 mL)
4. 4
   أخرىThe organic layer was separated
5. 5
   استخلاصThe aqueous layer was extracted with additional ether
6. 6
   workup.ADDITIONtreated with NaOH (2N, 880 mL) To the solution, H2O2 (30%, 136 mL)
7. 7
   workup.ADDITIONwas added dropwise while the reaction
8. 8
   درجة الحرارةwas cooled with an ice bath
9. 9
   workup.STIRRINGThe solution was stirred for 5-10 minutes
10. 10
    أخرىThe organic layer was separated
11. 11
    غسيلwashed with HCl (1N), saturated aqueous Na2S2O3, saturated aqueous NaHCO3, and brine
12. 12
    أخرىdried
13. 13
    تركيزconcentrated
14. 14
    أخرىThe residue was chromatographed on silica gel elating with 5-15% EtOAc/Hexane

الإجراء التجريبي

A solution of DME (24.39 mL, 235 mmol) in DCM (700 mL) under nitrogen atmosphere was cooled to −10° C., and diethylzinc (235 mL, 1M in hexane, 235 mmol) was added over 5-10 minutes followed by diiodomethane (37.9 mL, 469 mmol). The product from Example 34C (33.0 g, 122 mmol) in 100 mL DCM was added in 5-10 minutes. The temperature was maintained from −5° to −10° C. throughout the additions. The product from Example 34A, (E)-3-(4-bromophenyl)prop-2-en-1-ol (20 g, 94 mmol) in DCM (150 mL) was added dropwise, and the reaction mixture was stirred at ambient temperature for 16 hours. It was quenched with saturated aqueous NH4Cl (300 mL), HCl (1N, 480 mL) and diluted with ether (900 mL). The organic layer was separated. The aqueous layer was extracted with additional ether. The organic layers were is combined and treated with NaOH (2N, 880 mL) To the solution, H2O2 (30%, 136 mL) was added dropwise while the reaction was cooled with an ice bath. The solution was stirred for 5-10 minutes. The organic layer was separated, washed with HCl (1N), saturated aqueous Na2S2O3, saturated aqueous NaHCO3, and brine, dried and concentrated. The residue was chromatographed on silica gel elating with 5-15% EtOAc/Hexane to provide the title compound. 1H NMR (300 MHz, CDCl3): δ 0.92-1.0 (m, 2H), 1.45-1.48 (m, 2H), 1.76-1.85 (m, 1H), 3.61 (d, J=7.5 Hz, 2H), 6.95 (d, J=9 Hz, 2H), 7.37 (d, J=9 Hz, 2H). MS (DCl—NH3) m/z 228 (M+H)+. (ee 94%).

المصدر