Formaldehyde → (S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate

HRID 409812

Reaction equation

HRID 409812 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][C@H:5]([NH:9][C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C:6]([OH:8])=[O:7].[O:20]=[C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])N1C(OCC)=O.C=O.[CH3:38]C1C=CC(S(O)(=O)=O)=CC=1>CN1C(=O)CCC1.CCOC(C)=O.C1(C)C=CC=CC=1.CCOCC>[O:20]=[C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[N:1]1[CH2:2][CH2:3][CH2:4][C@H:5]1[C:6](=[O:8])[O:7][CH2:38][N:9]1[C:10]([O:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:11]

Participants

9

Reactant 4

HCID 712FormaldehydeHCID 6101p-Toluenesulfonic acidHCID 31187N-CarbethoxyphthalimideHCID 7010490N-alpha-Benzyloxycarbonyl-L-ornithine

Product 1

HCID 54380156(S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylateYield 76%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

(S)-5-amino-2-(benzyloxycarbonylamino)pentanoic acid (10.0 g, 37.56 mmol) and ethyl 1,3-dioxoisoindoline-2-carboxylate (9.04 g, 41.28 mmol) in NMP (40.0 mL) were heated to 150° C. for 30 min in 4 microwave reaction tubes. The mixture was diluted with EtOAc (500 mL). The organic mixture was washed with water (100 mL×2) and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give an oil, which was redissolved in toluene. To the resulting solution were added paraformaldehyde, PTSA and molecular sieves (3 A) and the mixture was heated to 150° C. for 20 min in a microwave reactor. The reaction mixture was diluted with ether (800 mL), washed with 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 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate (11.6 g, 76% for 2 steps).

Workup

  1. washThe organic mixture was washed with water (100 mL×2) and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give an oil, which
  6. washwashed with NaHCO3 and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified on silica gel using
  11. additiona mixture of EtOAc and hexanes

Sources & evidence

ORD record
ord-8dfdc3cb80874c57b1b82ff6040b4b5a
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Linked notes

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