Ethyl Acetate → (S)-tert-butyl 2-(4-azidophenyl)morpholine-4-carboxylate

HRID 710261Notes

Reaction equation

HRID 710261 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.N([O-])=O.[Na+].[N-:25]=[N+:26]=[N-].[Na+].C(OCC)(=O)C>C(O)(=O)C>[N:1]([C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1)=[N+:25]=[N-:26]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 66705988(S)-Tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate

Product 1

HCID 89689527(S)-tert-butyl 2-(4-azidophenyl)morpholine-4-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

(S)-tert-Butyl 2-(4-aminophenyl)morpholine-4-carboxylate (150 mg, 0.54 mol) was dissolved in 3 M acetic acid, then cooled to 0° C. Sodium nitrite (93 mg, 1.35 mmol) was added and the yellow solution was stirred at 0° C. for 5 min. Then sodium azide (70 mg, 1.08 mmol) was added to the mixture and stirring was continued for 15 min. Ethyl acetate was added to dissolve the precipitate and stirring was continued for 15 min. The organic layer was separated and the aqueous layer was re-extracted with ethyl acetate. The combined organic layers were extracted with 0.1M citric acid solution and with 1M sodium bicarbonate solution subsequently. After drying with MgSO4 the organic layer was evaporated to yield crude (S)-tert-butyl 2-(4-azidophenyl)morpholine-4-carboxylate as an yellow oil (161 mg) which was used for the following cycloaddition reaction.

Workup

  1. stirringstirring
  2. waitwas continued for 15 min
  3. dissolutionto dissolve the precipitate
  4. stirringstirring
  5. waitwas continued for 15 min
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was re-extracted with ethyl acetate
  8. extractionThe combined organic layers were extracted with 0.1M citric acid solution and with 1M sodium bicarbonate solution subsequently
  9. dry with materialAfter drying with MgSO4 the organic layer
  10. customwas evaporated

Sources & evidence

ORD record
ord-e4ccaa881b6344e3ad64cf24725683c3
Source dataset
uspto-grants-2015_11
Patent number
US09181230B2

Reaction notes

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