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

HRID 340918

Reaction equation

HRID 340918 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 1140TolueneSolvent2×HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

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

Workup

  1. washThe organic layer washed with water (100 mL×2), brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give an oil, which
  6. temperaturethe mixture was heated to 150° C. for 20 min
  7. washwashed with NaHCO3, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude was purified on silica gel column
  12. additiona mixture of EtOAc and hexanes

Sources & evidence

ORD record
ord-d905ed731ce9460db2768a56206d4a4c
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Linked notes

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