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

HRID 1098993

반응식

HRID 1098993 반응식
[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

참가 물질

7

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
60 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-5fcacf49044345ad805df19955720453
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08143290B2

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