Nitrogen → Di-tert-butyl 1-(2,6-difluoro-4-methoxyphenyl)hydrazine-1,2-dicarboxylate

HRID 1520967Notes

Reaction equation

HRID 1520967 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[F:11].[Li]CCCC.[N:17]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[N:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].N#N>C1COCC1>[F:11][C:3]1[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[C:7]([F:8])[C:2]=1[N:17]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[NH:18][C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20]

Participants

6

Reactant 4

HCID 947NitrogenHCID 97268Di-tert-butyl azodicarboxylateHCID 27249844-Bromo-3,5-difluoroanisoleHCID 178418339Butyllithium

Product 1

HCID 68157167Di-tert-butyl 1-(2,6-difluoro-4-methoxyphenyl)hydrazine-1,2-dicarboxylateYield 103.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In an oven-dried, N2-purged round bottom, 4-bromo-3,5-difluoroanisole (500 mg, 2.24 mmol) was dissolved in anhydrous THF (11 mL) and brought to −78° C. nBuLi (0.96 mL, 2.44 M in THF, 2.35 mmol) was added over 2 min. This was stirred for 5 min and then a solution di-tert-butyl azodicarboxylate (542 mg, 2.35 mmol) in anhydrous THF (3 mL) in an oven-dried, N2-purged pear flask was added in one portion via syringe. The reaction was removed from the ice bath and allowed to warm to room temperature over 30 min. The reaction, a clear solution, was quenched by the addition of aq. sat. NH4Cl. The material was extracted with two portions of ethyl acetate and the combined organics were dried over MgSO4 and concentrated in vacuo. Purification by silica gel flash chromatography (ethyl acetate in heptane) gave di-tert-butyl 1-(2,6-difluoro-4-methoxyphenyl)hydrazine-1,2-dicarboxylate (0.868 g, impure with ethyl acetate) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 6.48 (d, J=10.1 Hz, 2H) 3.73-3.85 (m, 3H) 1.36-1.60 (m, 18H).

Workup

  1. customIn an oven-dried, N2-purged round bottom
  2. custombrought to −78° C.
  3. additionwas added over 2 min
  4. additionwas added in one portion via syringe
  5. customThe reaction was removed from the ice bath
  6. customThe reaction
  7. customa clear solution, was quenched by the addition of aq. sat. NH4Cl
  8. extractionThe material was extracted with two portions of ethyl acetate
  9. dry with materialthe combined organics were dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customPurification by silica gel flash chromatography (ethyl acetate in heptane)

Sources & evidence

ORD record
ord-411cc326a5184aae89a8383016f738c6
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

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