تفاعل #80545

معادلة التفاعل

tert-butyl hydroxylamine

(R)-8-Fluoro-3-hydroxylamino-5-methoxy-3,4-dihydro-2H-1-benzopyran

sodium sulfate

NaHCO3

MeMgBr

Et2O

→

title compound

(R)-3-tert-Butylamino-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran

المذيبات

CS2

acetone

Acetone

ظروف التفاعل

المعالجة

1. 1
   أخرىa complete reaction
2. 2
   ترشيحThe salt was filtered off
3. 3
   workup.ADDITIONether (300 mL) was added to the filtrate
4. 4
   workup.ADDITIONthe solution, still containing finely suspended salt
5. 5
   ترشيحwas filtered through a sintered glass
6. 6
   ترشيحfilter (grade 4)
7. 7
   تركيزThe clear filtrate was concentrated in vacuo
8. 8
   تجفيفDry (sieves 3 Å) benzene (50 mL)
9. 9
   workup.ADDITIONwas added
10. 10
    تركيزthe resulting solution was concentrated in vacuo (finally on the pump)
11. 11
    workup.DISSOLUTIONThe glassy residue was dissolved
12. 12
    تجفيفin dry (sieves 3 Å) benzene (150 mL) under nitrogen
13. 13
    درجة الحرارةthe solution was cooled on an ice-bath (+4° C.)
14. 14
    أخرىthe internal temperature below +5° C.
15. 15
    workup.ADDITIONAfter the addition
16. 16
    أخرى(30 min)
17. 17
    workup.WAITThe cooling bath was taken away and 15 min
18. 18
    غسيلThe mixture was washed repeatedly with ether (3×150 mL)
19. 19
    غسيلwashed with brine
20. 20
    تجفيفdried (Na2SO4)
21. 21
    ترشيحfiltered
22. 22
    تركيزconcentrated in vacuo
23. 23
    أخرىFlash chromatography on silica [eluent: EtOAc (2 and 10%) in CHCl3 ] gave 2.9 g
24. 24
    workup.STIRRINGthe solution was stirred at room temperature for 4.5 h
25. 25
    أخرىThe solvent was evaporated in vacuo
26. 26
    أخرىto give an orange oil
27. 27
    workup.STIRRINGthe solution was stirred for a short time (15 min) at room temperature
28. 28
    أخرى(to precipitate elemental sulfur)
29. 29
    ترشيحfiltered
30. 30
    تركيزconcentrated
31. 31
    أخرىto give an oil
32. 32
    أخرىFlash chromatography on silica [eluent: EtOAc (10 to 25%) in hexane] gave

الإجراء التجريبي

(R)-8-Fluoro-3-hydroxylamino-5-methoxy-3,4-dihydro-2H-1-benzopyran (6.30 g, 29.6 mmol), anhydrous sodium sulfate (20 g) and acetone (500 mL) were refluxed under nitrogen for 4 days until TLC indicated a complete reaction. The salt was filtered off, ether (300 mL) was added to the filtrate and the solution, still containing finely suspended salt, was filtered through a sintered glass filter (grade 4). The clear filtrate was concentrated in vacuo. Dry (sieves 3 Å) benzene (50 mL) was added and the resulting solution was concentrated in vacuo (finally on the pump). The glassy residue was dissolved in dry (sieves 3 Å) benzene (150 mL) under nitrogen and the solution was cooled on an ice-bath (+4° C.). MeMgBr in Et2O (3.0M; 32.0 mL, 96 mmol) was added to the stirred solution above at a rate that kept the internal temperature below +5° C. (the reaction is exothermic). After the addition was complete (30 min) the solution was stirred at +4° C. for 0.5 h. The cooling bath was taken away and 15 min later the solution was poured on saturated NaHCO3 and ice (300 mL total). The mixture was washed repeatedly with ether (3×150 mL). The organic phases were combined, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Flash chromatography on silica [eluent: EtOAc (2 and 10%) in CHCl3 ] gave 2.9 g. of the tert-butyl hydroxylamine derivative. The latter was dissolved in CS2 (100 mL) under nitrogen and the solution was stirred at room temperature for 4.5 h. The solvent was evaporated in vacuo to give an orange oil. Acetone (approx. 50 mL) was added and the solution was stirred for a short time (15 min) at room temperature (to precipitate elemental sulfur), then filtered and concentrated to give an oil. Flash chromatography on silica [eluent: EtOAc (10 to 25%) in hexane] gave 2.34 g (31% total yield) of the title compound as a yellow oil. [α]21D =-82.8° (C=1; CHCl3). GC-MS (70 eV) M=253 (53%).

المصدر