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

HRID 629784Notes

Reaction equation

HRID 629784 reaction equation
[C:1]([O:4][CH2:5][C@H:6]1[N:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][C@@H:9]([CH2:19][O:20][C:21]2[C:26]([N+:27]([O-])=O)=[CH:25][CH:24]=[CH:23][C:22]=2[F:30])[O:8][CH2:7]1)(=[O:3])[NH2:2]>C(OCC)(=O)C>[NH2:27][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([F:30])[C:21]=1[O:20][CH2:19][C@H:9]1[O:8][CH2:7][C@@H:6]([CH2:5][O:4][C:1](=[O:3])[NH2:2])[N:11]([C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])[CH2:10]1

Participants

3

Reactant 1

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

Product 1

HCID 86726396(2S,5S)-tert-butyl 2-[(2-amino-6-fluorophenoxy)methyl]-5-[(carbamoyloxy)methyl]morpholine-4-carboxylateYield 53.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of the product from step 4 (1.4 g, 3.3 mmol) was dissolved in ethyl acetate (50 mL) and the solution was de-gassed with a stream of nitrogen for 10 min. To the degassed solution was added 5% palladium on charcoal (400 mg), and the mixture was stirred under a hydrogen atmosphere at ambient pressure for 16 h. The catalyst was removed by filtration through a celite pad, and the filter cake was washed with CH2Cl2 (200 mL). The filtrate solvents were removed under reduced pressure. The residue was purified on a 12 g SiO2 column using 20-50% EtOAc in hexanes to provide the product (700 mg) as a white solid. LC MS: RT=3.49 min, M+H=400 (6 min gradient).

Workup

  1. customthe solution was de-gassed with a stream of nitrogen for 10 min
  2. additionTo the degassed solution was added 5% palladium on charcoal (400 mg)
  3. customThe catalyst was removed by filtration through a celite pad
  4. washthe filter cake was washed with CH2Cl2 (200 mL)
  5. customThe filtrate solvents were removed under reduced pressure
  6. customThe residue was purified on a 12 g SiO2 column

Sources & evidence

ORD record
ord-da7d0384ec2f4c4184b8d7011d6d7195
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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