Acetic Acid → tert-Butyl 4-(3-fluoroanilino)piperidine-1-carboxylate

HRID 1724665Notes

Reaction equation

HRID 1724665 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].O=[C:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1.C(O)(=O)C.C([BH3-])#N.[Na+].[OH-].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH:5][CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 97423-FluoroanilineHCID 14798Sodium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 23137591tert-Butyl 4-(3-fluoroanilino)piperidine-1-carboxylateYield 64.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

3-fluoroaniline (40 g) was dissolved in MeOH and the solution was cooled to 0° C. Tert-butyl 4-oxo-1-piperidinecarboxylate (79 g, 1.1 eq), acetic acid (26.8 ml, 1.3 eq) and sodium cyanoborohydride (29 g, 1.3 eq, portionwise) were added successively to the solution. The reaction mixture was stirred at room temperature until completion. The reaction mixture was then cooled to 0° C. and an aqueous solution of NaOH (20%) was poured into the mixture (pH˜10). The precipitate was filtered off, washed with water, dried and recrystallised from iPrOH to give tert-butyl 4-(3-fluoroanilino)-1-piperidinecarboxylate 1 (68.5 g).

Workup

  1. temperatureThe reaction mixture was then cooled to 0° C.
  2. filtrationThe precipitate was filtered off
  3. washwashed with water
  4. customdried
  5. customrecrystallised from iPrOH

Sources & evidence

ORD record
ord-fbba24a45a394038b0381cc0d35bdb51
Source dataset
uspto-grants-2009_02
Patent number
US07488741B2

Reaction notes

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