Borane → tert-Butyl 4-aminomethyl-4-fluoropiperidine-1-carboxylate

HRID 1888078Notes

Reaction equation

HRID 1888078 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]#[N:16])([F:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B>C1COCC1>[NH2:16][CH2:15][C:11]1([F:14])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]1

Participants

4

Reactant 2

HCID 6331BoraneHCID 46242032Tert-butyl 4-cyano-4-fluoropiperidine-1-carboxylate

Product 1

HCID 40152119tert-Butyl 4-aminomethyl-4-fluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a 0° C. solution of 4-3 (8.83 g, 38.7 mmol) in 75 mL dry THF was added a solution of 1 M borane in THF (155 mL, 155 mmol) over 30 min. After 30 min more, the cold reaction was slowly quenched with EtOH (200 mL) and all solvent was removed in vacuo. The residue was taken up in saturated aq. NH4Cl/EtOAc (150 mL) and extracted with EtOAc (3×150 mL). The organic layers were washed with 1 N aq. NaOH, brine, dried over MgSO4, filtered, and concentrated in vacuo, giving crude 4-4 as a pale yellow oil. The crude amine 4-4 was carried forward. 1H NMR (CDCl3, 300 MHz): 3.94 (br, 2H), 3.08 (m, 2H), 1.85 (m, 2H), 1.51 (m, 4H), 1.44 (s, 9H); MS (Electrospray): m/z 218.2 (M−Me+H), 177.2 (M−t−Bu+H).

Workup

  1. customthe cold reaction
  2. customwas slowly quenched with EtOH (200 mL)
  3. customall solvent was removed in vacuo
  4. extractionextracted with EtOAc (3×150 mL)
  5. washThe organic layers were washed with 1 N aq. NaOH, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-effb230ba5484bcf830d4558f96835dd
Source dataset
uspto-grants-2013_08
Patent number
US08501773B2

Reaction notes

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