Water → (S)-2-Methyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

HRID 2200016Notes

Reaction equation

HRID 2200016 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8](Cl)=[O:9].[F:11][C:12]1[CH:13]=[CH:14][C:15]([NH:18][NH2:19])=[N:16][CH:17]=1.CCN(C(C)C)C(C)C.O>C(Cl)Cl.CCOCC.CCCCC>[F:11][C:12]1[CH:13]=[CH:14][C:15]([NH:18][NH:19][C:8]([N:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]2[CH3:1])=[O:9])=[N:16][CH:17]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 199167865-Fluoro-2-hydrazinylpyridineHCID 45081356(2S)-2-Methylpiperidine-1-carbonyl chloride

Product 1

HCID 86687104(S)-2-Methyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazideYield 77.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21877078Diethylether pentaneSolvent

Procedure

A stirred solution of Intermediate 2b (17.20 g, assumed to be 95.49 mmol) and (5-fluoro-pyridin-2-yl)-hydrazine (12.14 g, 95.51 mmol) in DCM (300 mL) at RT was treated with DIPEA (34 mL, 195.18 mmol) during 5 min. This mixture was continued to be stirred at RT for 4 days before being added to water (500 mL) and phases separated. The aqueous layer was further extracted into DCM (4×100 mL), combined extracts washed with brine, dried (MgSO4), passed through a phase separation cartridge and concentrated in vacuo to give a residual solid. This product was treated with Et2O-pentane and the resultant solids filtered off and dried to give Intermediate 2c (18.74 g, 77%). LCMS (Method 3) Rt 2.26 min, m/z 253 [MH+]. 1H NMR (300 MHz, CDCl3): 1.23 (3H, d, J 6.9), 1.40-1.74 (6H, m), 2.97 (1H, td, J 13.1, 3.0), 3.82-3.91 (1H, m), 4.27-4.38 (1H, m), 6.54 (1H, s), 6.78 (1H, ddd, J 9.1, 3.7, 0.6), 7.30 (1H, ddd, J 9.1, 7.8, 2.9), 8.00 (1H, d, J 2.6).

Workup

  1. customseparated
  2. extractionThe aqueous layer was further extracted into DCM (4×100 mL)
  3. washcombined extracts washed with brine
  4. dry with materialdried (MgSO4)
  5. custompassed through a phase separation cartridge
  6. concentrationconcentrated in vacuo
  7. customto give a residual solid
  8. filtrationthe resultant solids filtered off
  9. customdried

Sources & evidence

ORD record
ord-fea1acf6cdb64699bd8b3113a5fc66d6
Source dataset
uspto-grants-2016_06
Patent number
US09359354B2

Reaction notes

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