Santonox → (1S,2S,5S)-6-oxa-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid dibenzyl ester

HRID 1052119Notes

Reaction equation

HRID 1052119 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]=[CH:13][C@H:12]1[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=C(Cl)C=C(C(OO)=[O:34])C=1.S(C1C(C)=CC(O)=C(C(C)(C)C)C=1)C1C(C)=CC(O)=C(C(C)(C)C)C=1>ClCCCl>[CH2:19]([O:18][C:16]([C@H:12]1[N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:15][C@H:14]2[C@H:13]1[O:34]2)=[O:17])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 7308SantonoxHCID 70297m-Chloroperbenzoic acidHCID 11142303Dibenzyl (S)-2,5-dihydro-1H-pyrrole-1,2-dicarboxylate2×

Product 1

HCID 89428045(1S,2S,5S)-6-oxa-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid dibenzyl ester

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
90 °C

Procedure

Were prepared according to the procedure described in Tetrahedron, 1998, 54, 981-986 from (S)-2,5-dihydro-pyrrole-1,2-dicarboxylic acid dibenzyl ester. To a solution of (S)-2,5-dihydro-pyrrole-1,2-dicarboxylic acid dibenzyl ester (7.5 g, 22.23 mmol) in DCE (80 mL) were added mCPBA (7.67 g, 44.5 mmol) and 4,4′-thiobis(6-tert-butyl-m-cresol) (0.797 g, 2.22 mmol). The reaction mixture was then heated to 90° C. overnight. Then was concentrated. The crude residue was diluted in CH2Cl2 (200 mL) and washed with an aq. solution of Na2S2O5 5% and with a sat. aq. solution of NaHCO3. The organic layer was dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 8:2) give (1S,2S,5S)-6-oxa-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid dibenzyl ester: MS (UPLC/MS): 354 [M+H]+, tR (HPLC conditions b): 2.24 min and (1S,2S,5R)-6-oxa-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid dibenzyl ester: MS (UPLC/MS): 354 [M+H]+, tR (HPLC conditions b): 2.15 min.

Workup

  1. customWere prepared
  2. concentrationThen was concentrated
  3. additionThe crude residue was diluted in CH2Cl2 (200 mL)
  4. washwashed with an aq. solution of Na2S2O5 5% and with a sat. aq. solution of NaHCO3
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 8:2)

Sources & evidence

ORD record
ord-f25ef26bcd7a428e95756f98564a09ca
Source dataset
uspto-grants-2016_07
Patent number
US09388199B2

Reaction notes

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