1-Boc-1-methylhydrazine → ethyl 2-(2,3-difluoro-5-iodobenzoyl)-3-[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]prop-2-enoate

HRID 1168532Notes

Reaction equation

HRID 1168532 reaction equation
[F:1][C:2]1[C:19]([F:20])=[CH:18][C:17]([I:21])=[CH:16][C:3]=1[C:4]([C:6](=[CH:12]OCC)[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5].[CH3:22][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[NH2:24]>C(O)(C)(C)C>[F:1][C:2]1[C:19]([F:20])=[CH:18][C:17]([I:21])=[CH:16][C:3]=1[C:4]([C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:12][NH:24][N:23]([CH3:22])[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:5]

Participants

4

Reactant 2

HCID 37482801-Boc-1-methylhydrazineHCID 69879816Ethyl 2-(2,3-Difluoro-5-iodobenzoyl)-3-ethoxy-2-propenoate

Product 1

HCID 178472139ethyl 2-(2,3-difluoro-5-iodobenzoyl)-3-[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]prop-2-enoateYield 92.2%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Procedure

A solution of ethyl 2-(2,3-difluoro-5-iodobenzoyl)-3-ethoxy-2-propenoate (Preparation 21, 7.80 g) in tert-butanol (40 mL) is cooled with a cold water bath and a solution of tert-butyl 1-methylhydrazinecarboxylate (2.92 g) in tert-butanol (4 mL) is added. The cooling bath is removed, the mixture is stirred for 5 min at ambient temperature, and then is heated in an oil bath at 45° C. for 40 min. The reaction mixture is poured into 100 mL of crushed ice/water and extracted two times with ethyl acetate. The combined organic layers are dried (Na2SO4) and concentrated in vacuo. The crude product is purified by chromatography, using 300 g of silica gel, packed and eluted with EtOAc/heptane (1/3), to afford 8.95 g (92%) of the title compound as a yellow oily foam. Physical characteristics: 1H NMR (CDCl3) δ8.14, 8.07, 7.59-7.49, 7.46-7.41, 4.07, 3.30, 3.26, 1.50, 1.09, 0.97; MS (ESI+) m/z 511 (M+H)+.

Workup

  1. customThe cooling bath is removed
  2. temperatureis heated in an oil bath at 45° C. for 40 min
  3. additionThe reaction mixture is poured into 100 mL of crushed ice/water
  4. extractionextracted two times with ethyl acetate
  5. dry with materialThe combined organic layers are dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product is purified by chromatography
  8. washeluted with EtOAc/heptane (1/3)

Sources & evidence

ORD record
ord-64a0e742feee401781161d683297aaa4
Source dataset
uspto-grants-2003_09
Patent number
US06624159B2

Reaction notes

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