Hydrazine → tert-butyl N-(2-aminoethyl)-3-methyl-L-valinate

HRID 1174297Notes

Reaction equation

HRID 1174297 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][CH2:13][NH:14][C@H:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:16]([CH3:19])([CH3:18])[CH3:17].NN>C(O)C>[NH2:3][CH2:12][CH2:13][NH:14][C@H:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:16]([CH3:18])([CH3:19])[CH3:17]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 67407870tert-butyl(2S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3,3-dimethylbutanoate

Product 1

HCID 86599577tert-butyl N-(2-aminoethyl)-3-methyl-L-valinateYield 93.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
75 °C

Procedure

The product of Example 111-2 (87 g, 241.6 mmol) was taken up in ethanol (2 L) in a 3-necked, 3L round bottom flask equipped with mechanical stirring under N2. Hydrazine (anhydrous, 68.3 mL, 2.17 mol, 9 equivalents) was added. The reaction mixture was heated to 75° C., which resulted in the formation of a very thick suspension. The addition of more ethanol was necessary in order to continue effective stirring. The reaction was stirred for 1 hour at 75° C. until consumption of starting material was complete as determined by HPLC. The thick suspension was cooled to ambient temperature and quenched with 1 L of 0.5N NaOH solution. The mixture was diluted with 0.5N NaOH (2 L) and extracted with dichloromethane (2×2 L). The combined organic layer was washed with brine (1 L), dried over MgSO4, filtered and concentrated to oil. The oil was chased with heptanes to remove ethanol and pump dried to afford light yellow oil (50.2 g, 93.2% yield). 1H NMR (CDCl3): δ 2.73(m, 4H), 2.45(m, 1H), 1.64(s, 9H), 0.96(s, 9H).

Workup

  1. customequipped
  2. customwhich resulted in the formation of a very thick suspension
  3. stirringThe reaction was stirred for 1 hour at 75° C. until consumption of starting material
  4. temperatureThe thick suspension was cooled to ambient temperature
  5. customquenched with 1 L of 0.5N NaOH solution
  6. additionThe mixture was diluted with 0.5N NaOH (2 L)
  7. extractionextracted with dichloromethane (2×2 L)
  8. washThe combined organic layer was washed with brine (1 L)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated to oil
  12. customto remove ethanol and pump
  13. customdried

Sources & evidence

ORD record
ord-f6fbb4d3ee6148068649d2b86f1a743b
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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