Reaktion #41502

Reaktionsgleichung

isopropylmagnesium chloride

Magnesium

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

6-bromo-2,3-dihydrobenzofuran

iodine

→

subtitle compound

Ausbeute 36.3%

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

Ausbeute 36.3%

Lösungsmittel

THF

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe tube was sealed
2. 2
   Sonstigeflushed with argon
3. 3
   Temperaturto cool to r.t
4. 4
   Sonstigethe 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
    Sonstigeto reach r.t.
11. 11
    workup.STIRRINGstirred for 2 h
12. 12
    SonstigeThe 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
    SonstigeThe organic layer was separated
15. 15
    Waschenwashed with water and brine
16. 16
    Filtrationfiltered
17. 17
    Sonstigeevaporated
18. 18
    SonstigeThe product was purified by flash chromatography on silica with ethyl acetate/n-heptane (3:7)

Vorschrift

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.

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