HCID 22480752, compound → Tert-butyl 3-aminoazetidine-1-carboxylate

HRID 1279867Notes

Reaction equation

HRID 1279867 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1>CN.CO>[NH2:3][CH:12]1[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15]1

Participants

4

Reactant 1

HCID 22480752HCID 22480752, compound

Product 1

HCID 1516507Tert-butyl 3-aminoazetidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6329MethylamineSolvent

Procedure

A solution of tert-butyl 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-azetidinecarboxylate (Preparation 77) in methylamine in methanol (2M) (10 ml) was stirred in a sealed tube at 55° C. for 3 hours. On cooling a precipitate formed and the reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 ml) and washed with water (100 ml, containing (2M) hydrochloric acid (3 ml)) and water (50 ml, containing (2M) hydrochloric acid (2 ml)). The combined aqueous was basified with (2M) sodium hydroxide solution (20 ml) and extracted with ethyl acetate (3×75ml). The combined organic layers were dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of 97.5:2.5:0.25 (dichloromethane:methanol:ammonia) gradually changing to 90:10:1 (dichloromethane:methanol:ammonia) to afford the title compound (935 mg) of approximately 90% purity, which was used in preparation without further purification.

Workup

  1. temperatureOn cooling a precipitate
  2. customformed
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate (100 ml)
  5. washwashed with water (100 ml, containing (2M) hydrochloric acid (3 ml)) and water (50 ml, containing (2M) hydrochloric acid (2 ml))
  6. extractionextracted with ethyl acetate (3×75ml)
  7. dry with materialThe combined organic layers were dried over anhydrous magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of 97.5:2.5:0.25 (dichloromethane:methanol:ammonia)

Sources & evidence

ORD record
ord-b9ba27b1f8e346478322308d536bedc6
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

Loading…