tert-Butyl carbazate → N'-(2,6-dimethyl-pyridine-4-carbonyl)-hydrazinecarboxylic acid tert-butyl ester

HRID 1908848Notes

Reaction equation

HRID 1908848 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[N:10]=1)[C:5]([OH:7])=O.[C:12]([O:16][C:17]([NH:19][NH2:20])=[O:18])([CH3:15])([CH3:14])[CH3:13].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.CC(=O)OCC.C(OCC)C>[C:12]([O:16][C:17]([NH:19][NH:20][C:5]([C:4]1[CH:8]=[C:9]([CH3:11])[N:10]=[C:2]([CH3:1])[CH:3]=1)=[O:7])=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 70091tert-Butyl carbazateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 45318962,6-Dimethylpyridine-4-carboxylic acid

Product 1

HCID 67026924N'-(2,6-dimethyl-pyridine-4-carbonyl)-hydrazinecarboxylic acid tert-butyl esterYield 100.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21584169Diethylether ethylacetateSolvent

Procedure

To a solution of 2,6-dimethyl-isonicotinic acid (1.59 g, 10.5 mmol), hydrazinecarboxylic acid tert-butyl ester (1.42 g, 10.7 mmol) and DIPEA (6.06 g, 31.5 mmol) in DMF (33 mL), TBTU (4.05 g, 12.6 mmol) is added. The suspension is stirred at rt for 2 h before it is diluted with EA:diethyl ether 1:1 and washed with 1 N aq. NaOH solution. The washing is extracted three times with DCM, acidified and extracted again with DCM. The combined org. extracts are dried over MgSO4, filtered and concentrated to give crude N′-(2,6-dimethyl-pyridine-4-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (2.79 g) as a brown oil. This material is dissolved 5 M HCl in dioxane (14 mL) and the resulting solution is stirred at rt for 3 h. The solvent is removed in vacuo and the residue is purified by MPLC on RP-C18 silica gel to give 2,6-dimethyl-isonicotinic acid hydrazide hydrochloride (1.71 g) as a beige solid; LC-MS: tR=0.15 min, [M+1]+=166.10.

Workup

  1. washwashed with 1 N aq. NaOH solution
  2. extractionThe washing is extracted three times with DCM
  3. extractionextracted again with DCM
  4. dry with materialextracts are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a69c8693985d40298336805f75c2db7a
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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