Nitrogen → 1,1-Dimethylethyl (3R,4S)-4-amino-3-fluoro-1-piperidinecarboxylate

HRID 2280378Notes

Reaction equation

HRID 2280378 reaction equation
N#N.[F:3][CH:4]1[C:9](=O)[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]1.C([O-])(=O)C.[NH4+:22].[BH3-]C#[N:25].[Na+]>CO>[NH2:25][C@@H:9]1[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5][C@H:4]1[F:3].[NH2:22][C@H:9]1[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:12])[CH2:5][C@H:4]1[F:3]

Participants

7

Reactant 4

HCID 947NitrogenHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 10560711TERT-BUTYL 3-FLUORO-4-OXOPIPERIDINE-1-CARBOXYLATE

Product 2

HCID 112644351,1-Dimethylethyl (3R,4S)-4-amino-3-fluoro-1-piperidinecarboxylateHCID 45489895rac-tert-butyl (3R,4R)-4-amino-3-fluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of tert-butyl 3-fluoro-4-oxopiperidine-1-carboxylate (0.80 g, 3.68 mmol) in MeOH (10 mL) was added ammonium acetate (1.99 g, 25.80 mmol) and the resulting solution stirred at rt for 2 h. NaCNBH3 (0.29 g, 4.42 mmol) was then added and the solution stirred at rt overnight. The reaction mixture was concentrated to dryness and the organics extracted with EA from a 1% aq. solution of Na2CO3. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified with FC (CH2Cl2/MeOH, 9:1) to afford trans-tert-butyl 4-amino-3-fluoropiperidine-1-carboxylate and cis-tert-butyl 4-amino-3-fluoropiperidine-1-carboxylate both as colorless oils which solidified upon standing. LC-MS-conditions 08: tR=0.48 min; [M-CH3+H]+=204.25 and tR=0.46; [M+H]+=219.26; TLC: rf (CH2Cl2/MeOH, 9:1)=0.30 and 0.09.

Workup

  1. stirringthe solution stirred at rt overnight
  2. concentrationThe reaction mixture was concentrated to dryness
  3. extractionthe organics extracted with EA from a 1% aq. solution of Na2CO3
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified with FC (CH2Cl2/MeOH, 9:1)

Sources & evidence

ORD record
ord-7b3748a51cac4c6c8e9a2dd6784b74ce
Source dataset
uspto-grants-2015_09
Patent number
US09139524B2

Reaction notes

Loading…