Water → cis-2,6-Dimethyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

HRID 2200019Notes

Reaction equation

HRID 2200019 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.[CH3:10][C@H:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([CH3:17])[N:12]1[C:18](Cl)=[O:19].CCN(C(C)C)C(C)C.O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:18]([N:12]2[C@H:13]([CH3:17])[CH2:14][CH2:15][CH2:16][C@@H:11]2[CH3:10])=[O:19])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 199167865-Fluoro-2-hydrazinylpyridineHCID 94968704rac-(2R,6S)-2,6-dimethylpiperidine-1-carbonyl chloride

Product 1

HCID 86687154cis-2,6-Dimethyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazideYield 69.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (5-fluoro-pyridine-2-yl)-hydrazine (21.7 g, 171 mmol), Intermediate 3a (31.5 g, 180 mmol) and DIPEA (44.7 mmol, 256 mmol) in DCM (350 mL) was stirred at RT for 4 days. Water (350 mL) was added, then the aqueous layer extracted with DCM (100 mL). The combined organic extracts were passed through a hydrophobic fit and concentrated under vacuum to leave a solid. Trituration with diethyl ether/pentane (1:4, 150 mL), and drying under vacuum at 50° C., gave Intermediate 3b (31.7 g, 70%, ˜90% purity). LCMS: Rt 2.58 min, m/z 289 [MH+]. 1H NMR (300 MHz, CDCl3): 1.29 (6H, d, J=7.0 Hz), 1.45-1.89 (6H, m), 4.26 (2H, apparent quin, J=6.5 Hz), 6.53 (1H, s), 6.65 (1H, br s), 6.77 (1H, dd, J=9.0, 3.6 Hz), 7.29-7.28 (1H, ddd, J=9.0, 8.0, 3.0), 8.02 (1H, d, J=2.9 Hz).

Workup

  1. extractionthe aqueous layer extracted with DCM (100 mL)
  2. concentrationconcentrated under vacuum
  3. customto leave a solid
  4. dry with materialTrituration with diethyl ether/pentane (1:4, 150 mL), and drying under vacuum at 50° C.

Sources & evidence

ORD record
ord-59519a46778e4f15a4f760b0b9f90b38
Source dataset
uspto-grants-2016_06
Patent number
US09359354B2

Reaction notes

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