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

HRID 409813

Reaction equation

HRID 409813 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-a833270cf1844617be7ff9c495f4a1f7
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Linked notes

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