Iodine → 2-(N'-benzyloxycarbonyl-hydrazino)-2-methyl-propionic acid ethyl ester

HRID 2199437Notes

Reaction equation

[C:1]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=[O:4])[NH:2][NH2:3].Br[C:14]([CH3:21])([CH3:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16].N1C=CC=CC=1.II>CN(C=O)C.C(OCC)(=O)C>[CH2:18]([O:17][C:15](=[O:16])[C:14]([NH:3][NH:2][C:1]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4])([CH3:21])[CH3:20])[CH3:19]

Participants

Conditions

Temperature: 97.5 °C

Procedure

Benzyl carbazate (25 g, 0.15 mol) was dissolved in 50 mL of DMF in a round bottom flask. The solution was heated to 95-100° C. From two separate addition funnels, ethyl 2-bromoisobutyrate (58.5 g, 0.3 mol) and pyridine (29.7 g, 0.375 mol, 30 mL) were added drop-wise separately and simultaneously over 30-120 minutes. Heating was continued if necessary to propel the reaction to completion. The reaction was monitored by TLC (30% ethyl acetate in hexanes, I2 visualization). The mixture was allowed to cool, and then poured onto ice water. The aqueous mixture was extracted with ethyl ether, and the solvent was removed in vacuo. 2-(N′-benzyloxycarbonyl-hydrazino)-2-methyl-propionic acid ethyl ester was isolated, optionally after silica gel chromatography. 1H NMR (300 MHz, CDCl3) δ (ppm): 7.36 (br s, 5H), 6.6 (br s, 1H), 5.15 (br s, 2H), 4.2 (q, 2H), 1.3 (s, 6H), 1.25 (t, 3H). 1NMR analysis alone is insufficient to ascertain the extent of the reaction.

Workup

customFrom two separate
additionaddition funnels
temperatureHeating
customthe reaction to completion
temperatureto cool
additionpoured onto ice water
extractionThe aqueous mixture was extracted with ethyl ether
customthe solvent was removed in vacuo

Sources & evidence

ORD record: ord-b775ee51813540209a6647b6030a226c
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359289B2

Reaction notes

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