Water → Tert-butyl 2-[(4-cyano-2-fluorobenzyl)amino]-2-methylpropanoate

HRID 572571Notes

Reaction equation

[NH2:1][C:2]([CH3:11])([CH3:10])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[C:12]([C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[C:16]([F:22])[CH:15]=1)#[N:13].C([O-])(O)=O.[Na+].O>CN(C=O)C>[C:12]([C:14]1[CH:21]=[CH:20][C:17]([CH2:18][NH:1][C:2]([CH3:11])([CH3:10])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])=[C:16]([F:22])[CH:15]=1)#[N:13]

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of tert-butyl 2-amino-2-methylpropanoate (Bachem, 7.9 g, 0.05 mol) in dry DMF (50 mL) under nitrogen, was added 4-cyano-2-fluoro benzyl bromide (10.6 g, 0.05 mol) and NaHCO3 (8.3 g, 0.099 mol) as a solid. The reaction mixture was stirred for 16 h at 70° C. Water (70 mL) was added and extracted with ethyl acetate (100 mL). The organic layer was washed with water (3×100 mL) and the solvent was dried over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography using silica gel (60-120 mesh) and petroleum ether/ethyl acetate as eluent, affording the title compound as colourless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.78 (d, J=10.0 Hz, 1H), 7.71-7.65 (m, 2H), 3.69 (d, J=6.9 Hz, 2H), 2.55 (s, 1H), 1.44 (s, 9H), 1.19 (s, 6H).

Workup

extractionextracted with ethyl acetate (100 mL)
washThe organic layer was washed with water (3×100 mL)
dry with materialthe solvent was dried over Na2SO4
concentrationconcentrated under vacuum
customThe residue was purified by column chromatography

Sources & evidence

ORD record: ord-5eb3120338d546299752ed8651e6229a
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029405B2

Reaction notes

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