N-Hydroxyphthalimide → HCID 57999185, compound

HRID 1917468Notes

Reaction equation

HRID 1917468 reaction equation
[OH:1][CH2:2][CH:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.O[N:17]1C(=O)C2C(=CC=CC=2)C1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.O.NN>C(Cl)Cl.O>[NH2:17][O:1][CH2:2][CH:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1

Participants

8

Reactant 5

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 24654Hydrazine hydrate (1:1)HCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 5201202tert-Butyl 2-(hydroxymethyl)morpholine-4-carboxylate

Product 1

HCID 57999185HCID 57999185, compoundYield 56.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate (5 g, 23 mmol) in CH2Cl2 (250 mL) was added 2-hydroxyisoindoline-1,3-dione (5.6 g, 34.5 mmol) and triphenylphosphine (15 g, 57.5 mmol). The resultant mixture was cooled to 0° C. and diisopropyl azodicarboxylate (11.1 ml, 57.5 mmol) was slowly added dropwise with an addition funnel under N2 atmosphere. The reaction mixture was stirred at ambient temperature for 48 h. To the reaction mixture H2O (300 mL) was added and extracted with CH2Cl2. The organic layers were washed with brine. Dried over anhydrous MgSO4, filtered and concentrated to provide clear oil, which was purified by flash chromatography (50% EtOAc-Hexane). The resultant clear oily compound 2S was dissolved in CHCl3:CH3OH (50 ml). Hydrazine hydrate (25 mL, 0.25 mol) was added. The reaction mixture was stirred at ambient temperature overnight. The resultant solid was filtered off and the filtrate concentrated under reduced pressure to provide a clear oil, which was purified by flash chromatography (10% CH3OH—CH2Cl2) to afford 3 g (56%, over two steps) of tert-butyl 2-(aminooxymethyl)morpholine-4-carboxylate (2T) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.47 (s, 9H) 3.46-3.62 (m, 2H) 3.61-3.79 (m, 4H) 3.79-4.04 (m, 3H). [M+H] calc'd for C10H20N2O4, 233; found, 233.

Workup

  1. extractionextracted with CH2Cl2
  2. washThe organic layers were washed with brine
  3. dry with materialDried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto provide clear oil, which
  7. customwas purified by flash chromatography (50% EtOAc-Hexane)
  8. dissolutionThe resultant clear oily compound 2S was dissolved in CHCl3
  9. stirringThe reaction mixture was stirred at ambient temperature overnight
  10. filtrationThe resultant solid was filtered off
  11. concentrationthe filtrate concentrated under reduced pressure
  12. customto provide a clear oil, which
  13. customwas purified by flash chromatography (10% CH3OH—CH2Cl2)

Sources & evidence

ORD record
ord-1ebc53d694884be6ac28d66cb3c4a013
Source dataset
uspto-grants-2013_12
Patent number
US08618290B2

Reaction notes

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