Hydrochloric Acid → 4-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1838864Notes

Reaction equation

HRID 1838864 reaction equation
[CH3:1][N:2]([C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)[NH2:3].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[BH3-]C#N.[Na+].Cl.C(=O)(O)[O-].[Na+]>C(O)C>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([NH:3][N:2]([C:4](=[O:13])[CH2:5][C:6]2[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=2)[CH3:1])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 59120453(4-fluorophenyl)-acetic acid N-methyl-hydrazide

Product 1

HCID 600611354-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-hydrazino}-piperidine-1-carboxylic acid tert-butyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of (4-fluorophenyl)-acetic acid N-methyl-hydrazide, 8, (2 g, 11 mmol) in ethanol (20 mL) is added commercially available 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (2.19 g, 11 mmol). The reaction mixture is refluxed for 30 minutes, then cooled to room temperature after which NaCNBH3 (1.04 g, 16,5 mmol) is added. The pH of the reaction mixture is adjusted to about 3 with concentrated HCl and the reaction mixture stirred for 3 hours at room temperature. The mixture is neutralized with saturated sodium bicarbonate and extracted three times with CH2Cl2. The combined organic layers are dried, filtered and concentrated in vacuo. Purification over silica (EtOAc) affords 3.7 g (93% yield) of the desired product. ESI/MS: 366.3 (M+H).

Workup

  1. temperatureThe reaction mixture is refluxed for 30 minutes
  2. additionis added
  3. extractionextracted three times with CH2Cl2
  4. customThe combined organic layers are dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification over silica (EtOAc)

Sources & evidence

ORD record
ord-05754addf31a44d3be1c1fa90529b504
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

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