Ammonium formate → rac-tert-butyl (3R,4R)-4-amino-3-fluoropiperidine-1-carboxylate

HRID 2280386Notes

Reaction equation

HRID 2280386 reaction equation
[N:1]([C@@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@H:5]1[F:17])=[N+]=[N-].C([O-])=O.[NH4+]>CO.[Pd]>[NH2:1][C@@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:6][C@H:5]1[F:17]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 73977892HCID 73977892, compound

Product 1

HCID 45489895rac-tert-butyl (3R,4R)-4-amino-3-fluoropiperidine-1-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 0.59 g (2.42 mmol) of trans-4-azido-1-Boc-3-fluoropiperidine 4 in 10 mL of MeOH was added 0.61 g (9.67 mmol) of ammonium formate and 0.25 g (0.24 mmol Pd) of 10% Pd on carbon. The reaction mixture was stirred under N2-atmosphere at 50° C. for 5 h. After cooling, the mixture was filtered over diatomaceous earth and evaporated under reduced pressure. The crude mixture was then subjected to flash silicagel chromatography (5% Et3N in EtOAc, short path column) to give 0.42 g (80%) of trans-4-amino-1-Boc-3-fluoropiperidine 5 as an oil. 1H NMR (CDCl3): δ 1.39 (9H, s); 1.60 (2H, s(br)); 1.76-1.86 (1H, m); 2.65-2.76 (2H, m); 2.78-2.90 (2H, m); 3.89-3.97 (1H, m); 4.01 (1H, dm, J=48.5 Hz); 4.15-4.30 (1H, m). 19F NMR (CDCl3): δ −191.0 to −190.3 (1F, m). 13C NMR (CDCl3): δ 28.4 (3×), 31.8, 41.9 (br), 46.2 (br), 53.5 (d, J=18.5 Hz), 80.3, 93.0 (d, J=177.7 Hz), 154.6. IR (ATR, cm−1): ν=1685, 1415, 1244, 1152, 1028. MS (ES+) m/z (%): 204 (M-CH3+H+), 163 (M−3CH3+2H+, 100).

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered over diatomaceous earth
  3. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-f4366df05a594a6a833ff86dd2afda53
Source dataset
uspto-grants-2015_09
Patent number
US09139523B2

Reaction notes

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