N-Hydroxyphthalimide → tert-butyl 3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)oxy]pyrrolidine-1-carboxylate

HRID 1821816Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1821816
[OH:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.O[N:15]1[C:19](=[O:20])[C:18]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:17]2[C:16]1=[O:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[O:25]=[C:16]1[C:17]2[C:18](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19](=[O:20])[N:15]1[O:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1

Komponenten

6

Edukt 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 44169391-Boc-3-pyrrolidinol

Produkt 1

HCID 19691445tert-butyl 3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)oxy]pyrrolidine-1-carboxylateAusbeute 52,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To an ice-cold solution of tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1.0 g, 5.5 mmol), N-hydroxyphthalimide (0.90 g, 5.5 mmol) and triphenylphosphine (1.4 g, 5.5 mmol) in THF (30 mL) was added a solution of diethyl azodicarboxylate (0.96 mL, 6.1 mmol) in THF (5 mL) dropwise. The stirred reaction mixture was allowed to warm to ambient temperature. After 3 days, most of the THF was removed under reduced pressure. The residue was partitioned between CH2Cl2 (40 mL) and H2O (30 mL). The organic layer was separated and washed with saturated NaCl (20 mL), dried (Na2SO4) and concentrated under reduced pressure. Purification by column chromatography (silica gel, 75:25 hexanes/EtOAc to 50:50 hexanes/EtOAc) gave tert-butyl 3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)oxy]pyrrolidine-1-carboxylate (0.96 g, 52%): 1H NMR (300 MHz, CDCl3) δ1.49 (9H, s), 1.97-2.20 (1H, s), 2.25-2.31 (1H, m), 3.53-3.78 (4H, m), 4.95-5.00 (1H, m), 7.75-7.87 (4H, m).

Aufarbeitung

  1. customThe stirred reaction mixture
  2. custommost of the THF was removed under reduced pressure
  3. customThe residue was partitioned between CH2Cl2 (40 mL) and H2O (30 mL)
  4. customThe organic layer was separated
  5. washwashed with saturated NaCl (20 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by column chromatography (silica gel, 75:25 hexanes/EtOAc to 50:50 hexanes/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-88acb3bb8af345ab830194b48b408bca
Quelldatensatz
uspto-grants-2009_10
Patentnummer
US07608627B2

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