Homoallyl bromide → Diethyl 2-(but-3-enyl)-2-(tert-butoxycarbonylamino)malonate

HRID 579510

Reaction equation

HRID 579510 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][CH:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:23][CH2:24][CH:25]=[CH2:26]>>[CH2:26]([C:11]([NH:10][C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:25][CH:24]=[CH2:23]

Participants

4

Reactant 3

HCID 21241Homoallyl bromideHCID 24758Sodium hydrideHCID 382219Diethyl 2-((tert-butoxycarbonyl)amino)malonate

Product 1

HCID 86663717Diethyl 2-(but-3-enyl)-2-(tert-butoxycarbonylamino)malonateYield 90.1%

Conditions

Temperature
90 °C

Procedure

To a suspension of sodium hydride (8.7 g, 218 mmol, 60% suspension) in dimethylformaamide (250 mL) at 0° C. was added diethyl 2-(tert-butoxycarbonylamino)malonate (50.0 g, 182 mmol) in dimethylformaamide (250 mL). After stirring for 30 minutes, 4-bromobut-1-ene (29.5 g, 218 mmol, 22.2 mL) was added and the mixture was warmed to 90° C. After stirring an additional 4 h, the solution was cooled to room temperature and the solvents were removed by evaporation. The resulting residue was diluted with ethyl acetate (1.0 L), washed successively with water (2×250 mL), saturated aqueous sodium chloride (1×200 mL) and concentrated. Purification using a combiflash system (330 g silica column, eluted with 15-50% ethyl acetate in heptanes) gave diethyl 2-(but-3-enyl)-2-(tert-butoxycarbonylamino)malonate (54 g, 90%). 1H NMR (CDCl3) δ 5.92 (bs, 1H), 5.79-5.71 (m, 1H), 5.03-4.93 (m, 2H), 4.24-4.19 (m, 4H), 2.36 (m, 2H), 1.96-1.93 (m, 2H), 1.42 (s, 9H), 1.27-1.24 (m, 6H).

Workup

  1. stirringAfter stirring an additional 4 h
  2. temperaturethe solution was cooled to room temperature
  3. customthe solvents were removed by evaporation
  4. additionThe resulting residue was diluted with ethyl acetate (1.0 L)
  5. washwashed successively with water (2×250 mL), saturated aqueous sodium chloride (1×200 mL)
  6. concentrationconcentrated
  7. customPurification
  8. washa combiflash system (330 g silica column, eluted with 15-50% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-ebf75e7513a94ce7ba6830488ce2ab1f
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Linked notes

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