Iodine → (R)-t-butyl 1-(2,3-dihydrobenzofuran-6-yl)-1-oxopropan-2-ylcarbamate

HRID 13224

Reaction equation

HRID 13224 reaction equation
[Mg].Br[C:3]1[CH:11]=[CH:10][C:6]2[CH2:7][CH2:8][O:9][C:5]=2[CH:4]=1.II.CON(C)[C:17](=[O:28])[C@@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:19].C([Mg]Cl)(C)C>O1CCCC1>[O:9]1[C:5]2[CH:4]=[C:3]([C:17](=[O:28])[C@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])[CH3:19])[CH:11]=[CH:10][C:6]=2[CH2:7][CH2:8]1

Participants

7

Reactant 5

HCID 807IodineHCID 5462224MagnesiumHCID 112526166-Bromo-2,3-dihydro-1-benzofuranHCID 11806530(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamateHCID 178418918HCID 178418918, compound

Product 1

HCID 59339724(R)-t-butyl 1-(2,3-dihydrobenzofuran-6-yl)-1-oxopropan-2-ylcarbamateYield 36.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

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.

Workup

  1. customThe tube was sealed
  2. customflushed with argon
  3. temperatureto cool to r.t
  4. customthe cooling bath was removed
  5. stirringStirring
  6. waitwas continued for 10 min
  7. additionThen the preformed Grignard reagent was added in small portions
  8. stirringwith stirring
  9. additionAfter the addition the mixture
  10. customto reach r.t.
  11. stirringstirred for 2 h
  12. customThe solvent was evaporated
  13. additionthe mixture was poured into an ice-cold ethyl acetate (150 ml) and aq. HCl (1M, 35 ml) mixture
  14. customThe organic layer was separated
  15. washwashed with water and brine
  16. filtrationfiltered
  17. customevaporated
  18. customThe product was purified by flash chromatography on silica with ethyl acetate/n-heptane (3:7)

Sources & evidence

ORD record
ord-870de5e72f1c4e5b8416f7b114eb8b0a
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Linked notes

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