Ammonium formate → Tert-butyl 2-(4-amino-3-fluorophenyl)morpholine-4-carboxylate

HRID 571810Notes

Reaction equation

HRID 571810 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([N:20]=C(C3C=CC=CC=3)C3C=CC=CC=3)=[C:16]([F:34])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([F:34])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 2723923Ammonium formateHCID 86671396(RS)-2-[4-(benzhydrylidene-amino)-3-fluoro-phenyl]-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68325450Tert-butyl 2-(4-amino-3-fluorophenyl)morpholine-4-carboxylateYield 99.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of (RS)-2-[4-(benzhydrylidene-amino)-3-fluoro-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (2.21 g) in methanol (40 ml) was added ammonium formate (4.54 g). The reaction mixture was degassed by bubbling argon into the mixture for several minutes. 10% Palladium on activated charcoal (255 mg) was then added and the reaction mixture was stirred at 60° C. for 1 hour. The reaction mixture was then filtered through celite and the filtrate was poured into 1 M aq. NaOH and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 30% EtOAc in hexanes) to afford (RS)-2-(4-amino-3-fluoro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (1.42 g, 74%) as a white solid. MS (ISP): 319.2 ([M+Na]+), 297.3 ([M+H]+), 241.2 ([M+H—C4H8]+), 197.2 ([M+H—C4H8—CO2]+).

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling argon into the mixture for several minutes
  3. addition10% Palladium on activated charcoal (255 mg) was then added
  4. filtrationThe reaction mixture was then filtered through celite
  5. additionthe filtrate was poured into 1 M aq. NaOH
  6. extractionextracted twice with EtOAc
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography (silica gel; gradient: 0% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-eeb5758671c64283bedd2a9d8c733d77
Source dataset
uspto-grants-2015_05
Patent number
US09029370B2

Reaction notes

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