Hydrochloric Acid → (S)-benzyl 5-(1,3-dioxoisoindolin-2-yl)-1-hydroxypentan-2-yl(methyl)carbamate

HRID 416382

反応式

HRID 416382 の反応式
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][C@H:15]1[C:19](=O)[O:18][CH2:17][N:16]1[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].[SiH](CC)(CC)CC.ClC(OC(C)(C)C)=O.Cl>C(Cl)Cl>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][CH2:14][C@H:15]([N:16]([CH3:17])[C:21](=[O:22])[O:23][CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[CH2:19][OH:18]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 12052TriethylsilaneHCID 9920397Tert-butyl ChloroformateHCID 54380156(S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate

生成物 1

HCID 57947404(S)-benzyl 5-(1,3-dioxoisoindolin-2-yl)-1-hydroxypentan-2-yl(methyl)carbamate収率 45%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate (11.6 g, 28.40 mmol) in DCM (30.0 mL) was added Et3SiH (13.6 mL, 85.3 mmol). The reaction mixture was stirred overnight, concentrated under reduced pressure, and dissolved in THF (100 mL). To the resulting solution was added tert-butyl chloroformate (4.4 mL, 34.08 mmol) and TEA (12.0 mL, 85.2 mmol) at 0° C. The reaction mixture was stirred at RT for 30 min. The precipitate was filtered off and the filtrate was added into a suspension of NaBH4 in water (1.0 mL) at 0° C. The reaction mixture was stirred at RT for 30 min. LCMS indicated the completion of the reaction. The reaction mixture was acidified to pH 3 by HCl (1N) and extracted with EtOAc (300 mL×2). The combined organic layers were washed with saturated NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel using a mixture of EtOAc and hexanes to give (S)-benzyl 5-(1,3-dioxoisoindolin-2-yl)-1-hydroxypentan-2-yl(methyl)carbamate (5.01 g, 45%). LRMS (M+H+) m/z 397.3.

後処理

  1. concentrationconcentrated under reduced pressure
  2. dissolutiondissolved in THF (100 mL)
  3. stirringThe reaction mixture was stirred at RT for 30 min
  4. filtrationThe precipitate was filtered off
  5. additionthe filtrate was added into a suspension of NaBH4 in water (1.0 mL) at 0° C
  6. stirringThe reaction mixture was stirred at RT for 30 min
  7. customthe completion of the reaction
  8. extractionextracted with EtOAc (300 mL×2)
  9. washThe combined organic layers were washed with saturated NaHCO3 and brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified on silica gel using
  14. additiona mixture of EtOAc and hexanes

出典と根拠

ORDレコード
ord-338156c3c233425a92ebaba9660e5d34
出典データセット
uspto-grants-2012_01
特許番号
US08088793B2

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