Pyridine → (2S,5S)-tert-butyl 5-[(carbamoyloxy)methyl]-2-[(2-fluoro-6-nitrophenoxy)methyl]morpholine-4-carboxylate

HRID 629783Notes

Reaction equation

HRID 629783 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[C:3]=1[O:4][CH2:5][C@H:6]1[O:11][CH2:10][C@@H:9]([CH2:12][OH:13])[N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]1.C(C1NC=CN=1)(C1NC=CN=1)=[O:29].[N:40]1[CH:45]=CC=CC=1>>[C:45]([O:13][CH2:12][C@H:9]1[N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:18])[CH3:19])=[O:15])[CH2:7][C@@H:6]([CH2:5][O:4][C:3]2[C:21]([N+:25]([O-:27])=[O:26])=[CH:22][CH:23]=[CH:24][C:2]=2[F:1])[O:11][CH2:10]1)(=[O:29])[NH2:40]

Participants

4

Reactant 3

HCID 1049PyridineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 86726395(2S,5R)-tert-butyl 2-[(2-fluoro-6-nitrophenoxy)methyl]-5-(hydroxymethyl)morpholine-4-carboxylate

Product 1

HCID 86726394(2S,5S)-tert-butyl 5-[(carbamoyloxy)methyl]-2-[(2-fluoro-6-nitrophenoxy)methyl]morpholine-4-carboxylate

Conditions

Temperature
60 °C

Procedure

To a solution of the product from step 3 (1.6 g, 4.1 mmol) in pyridine (12 mL) was added carbonyl diimidazole (2.0 g, 12.3 mmol) and the mixture was heated in a sealed tube at 60° C. for 2 h. The reaction mixture was cooled to ambient temperature and NH3 gas was bubbled into the solution for 5 min, and the mixture was heated in a sealed tube at 60° C. for 16 h. The reaction was cooled to ambient temperature and the solvent was concentrated under reduced pressure. The residue was purified on a 24 g SiO2 column using a gradient elution of 20-70% EtOAc in hexanes. Fractions containing product were combined and the solvents were removed under reduced pressure to provide the product (1.4 g) as a colorless oil. LC MS: RT=3.60 min, M+H=430 (6 min gradient).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customNH3 gas was bubbled into the solution for 5 min
  3. temperaturethe mixture was heated in a sealed tube at 60° C. for 16 h
  4. temperatureThe reaction was cooled to ambient temperature
  5. concentrationthe solvent was concentrated under reduced pressure
  6. customThe residue was purified on a 24 g SiO2 column
  7. washa gradient elution of 20-70% EtOAc in hexanes
  8. additionFractions containing product
  9. customthe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-8f48b5e9762246e7a812cd26fc917204
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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