反応 #41502

反応方程式

isopropylmagnesium chloride

Magnesium

(S)-tert-butyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamate

6-bromo-2,3-dihydrobenzofuran

iodine

→

subtitle compound

収率 36.3%

(R)-t-Butyl 1-(2,3-dihydrobenzofuran-6-yl)-1-oxopropan-2-ylcarbamate

収率 36.3%

溶媒

THF

tetrahydrofuran

反応条件

後処理

1. 1
   その他The tube was sealed
2. 2
   その他flushed with argon
3. 3
   温度to cool to r.t
4. 4
   その他the cooling bath was removed
5. 5
   workup.STIRRINGStirring
6. 6
   workup.WAITwas continued for 10 min
7. 7
   workup.ADDITIONThen the preformed Grignard reagent was added in small portions
8. 8
   workup.STIRRINGwith stirring
9. 9
   workup.ADDITIONAfter the addition the mixture
10. 10
    その他to reach r.t.
11. 11
    workup.STIRRINGstirred for 2 h
12. 12
    その他The solvent was evaporated
13. 13
    workup.ADDITIONthe mixture was poured into an ice-cold ethyl acetate (150 ml) and aq. HCl (1M, 35 ml) mixture
14. 14
    その他The organic layer was separated
15. 15
    洗浄washed with water and brine
16. 16
    ろ過filtered
17. 17
    その他evaporated
18. 18
    その他The product was purified by flash chromatography on silica with ethyl acetate/n-heptane (3:7)

実験手順

Magnesium (711 mg, 29.3 mmol) was placed in a screw-cap reaction tube, and a solution of 6-bromo-2,3-dihydrobenzofuran (4.16 g, 20.9 mmol) in tetrahydrofuran (30 mL) was added, followed by a small crystal of iodine. The tube was sealed and flushed with argon. The mixture was heated at 60° C. for 1 h, and then the reaction mixture was allowed to cool to r.t. A slurry of (S)-tert-butyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamate (4.85 g, 20.9 mmol) in THF (20 ml) was cooled on a acetone/ice bath to −10° C., and a solution isopropylmagnesium chloride (2 M in THF, 10.5 mL, 21 mmol) was slowly added. The mixture was stirred for 15 min, the cooling bath was removed. Stirring was continued for 10 min. Then the preformed Grignard reagent was added in small portions with stirring. After the addition the mixture was allowed to reach r.t. and stirred for 2 h. The solvent was evaporated, and the mixture was poured into an ice-cold ethyl acetate (150 ml) and aq. HCl (1M, 35 ml) mixture. The organic layer was separated, washed with water and brine, filtered, and evaporated. The product was purified by flash chromatography on silica with ethyl acetate/n-heptane (3:7) to give 2.21 g (36%) of the subtitle compound.

出典