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

HRID 416349

反応式

HRID 416349 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.C1COCC1>[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

7

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 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran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. The mixture was concentrated under reduced pressure and dissolved in THF (100 mL). To this THF solution was added tert-butyl chloroformate (4.4 mL, 34.08 mmol) at 0° C. followed by TEA (12.0 mL, 85.2 mmol) and stirred at RT for 30 min. The precipitate was filtered off and the filtrate was added into a NaBH4 suspension in water (1.0 mL) at 0° C., and the mixture was stirred at RT for 30 min. LC/MS indicated the completion of the reaction. The mixture was acidified to pH 3 using HCl (1 N). The aqueous layer was extracted with EtOAc (300 mL×2). The combined organic layer was washed with NaHCO3, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified on silica gel column 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. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutiondissolved in THF (100 mL)
  3. stirringstirred at RT for 30 min
  4. filtrationThe precipitate was filtered off
  5. additionthe filtrate was added into a NaBH4 suspension in water (1.0 mL) at 0° C.
  6. stirringthe mixture was stirred at RT for 30 min
  7. customthe completion of the reaction
  8. extractionThe aqueous layer was extracted with EtOAc (300 mL×2)
  9. washThe combined organic layer was washed with NaHCO3, brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude was purified on silica gel column
  14. additiona mixture of EtOAc and hexanes

出典と根拠

ORDレコード
ord-00fdc242d09a46a6805cc11fd1e26b63
出典データセット
uspto-grants-2012_01
特許番号
US08088793B2

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