Hydrazine hydrate (1:1) → (4-Tert-butoxy-3,6-difluoro-5-methoxypyridin-2-yl)hydrazine

HRID 983399Notes

Reaction equation

HRID 983399 reaction equation
[C:1]([O:5][C:6]1[C:11]([O:12][CH3:13])=[C:10]([F:14])[N:9]=[C:8](F)[C:7]=1[F:16])([CH3:4])([CH3:3])[CH3:2].O.[NH2:18][NH2:19]>C(O)CC>[C:1]([O:5][C:6]1[C:11]([O:12][CH3:13])=[C:10]([F:14])[N:9]=[C:8]([NH:18][NH2:19])[C:7]=1[F:16])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 104899104-t-Butoxy-2,3,6-trifluoro-5-methoxypyridine

Product 1

HCID 22560377(4-Tert-butoxy-3,6-difluoro-5-methoxypyridin-2-yl)hydrazineYield 90%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Procedure

A mixture of 4-tert-butoxy-2,3,6-trifluoro-5-methoxypyridine (1.5 g. 6.4 mmol) and hydrazine monohydrate (1.7 mL, 34 mmol [Qun Li et al. J. Med. Chem. 1996, 39(16), 3070-3088]) in n-propanol (10 mL) was heated to reflux for 3 hours. The solvent was removed in vacuo and the residue was dissolved in dichlromethane, washed with water and concentrated to afford crude (4-tert-butoxy-3,6-difluoro-5-methoxypyridin-2-yl)hydrazine (1.4 g, 90%). 1.2 g of the material was redissolved in methanol (12 mL) and 20% aqueous sodium hydroxide (2.5 mL). Oxygen was passed through the solution with vigorous stirring for 20 hours. The deep blue solution was diluted with water (12 mL) and extracted with hexane (2×30 mL). The combined organics were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography, eluting with ethyl acetate/hexane (1:16) to afford the title compound (0.9 g). 1H NMR (400 MHz, CDCl3) δ 7.74 (m, 1H), 3.93 (m, 3H), 1.41 (s, 9H). MSCI: m/z=218 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 3 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in dichlromethane
  5. washwashed with water
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f0e44416de1541608b67ab8845d03c67
Source dataset
uspto-grants-2005_03
Patent number
US06864259B2

Reaction notes

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