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

HRID 2403300Notes

Reaction equation

HRID 2403300 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)[CH:9]1C(C)(C)C)=[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 123444150HCID 123444150, compound

Product 1

HCID 68325450Tert-butyl 2-(4-amino-3-fluorophenyl)morpholine-4-carboxylateYield 112%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of tert-butyl (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-c2a20b4f92d14cebae6592717a2ba1f3
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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