Sodium hydride → methyl N-(3-chloro-4-fluorophenyl)-N-(3-methoxybenzyl)alaninate

HRID 1822179Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C@H:10]([C:12]([O:14][CH3:15])=[O:13])[CH3:11])[CH:5]=[CH:6][C:7]=1[F:8].[I-].C([NH3+])(C)(C)C.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27]Br.[H-].[Na+]>C([O-])(O)=O.[Na+].CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:27][C:26]2[CH:29]=[CH:30][CH:31]=[C:24]([O:23][CH3:22])[CH:25]=2)[C@H:10]([C:12]([O:14][CH3:15])=[O:13])[CH3:11])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

Conditions

Temperature: 60 °C

Procedure

To a flask containing anhydrous DMF (150 mL) was added 1-3 (2.00 g, 8.633 mmol), tertbutylammonium iodide (0.319 g. 0.863 mmol) and 3-methoxy-benzyl bromide (4.340 g, 21.583 mmol) followed by NaH (0.269 g, 11.223 mmol). The resulting solution was heated at 60° C. for 4 days. Upon completion, the reaction mixture was diluted with NaHCO3 (sat. aq), and extracted with ethyl acetate (3×75 mL). The combined organic layers were dried with Na2SO4, filtered, and concentrated. The crude residue was purified by flash column chromatography (SiO2 0-40% ethyl acetate/hexanes gradient) to yield methyl N-(3-chloro-4-fluorophenyl)-N-(3-methoxybenzyl)alaninate (6-1). 1H NMR (300 MHz, CDCl3) δ 7.26 (m, 2H), 6.85 (m, 4H), 6.58 (m, 1H), 4.51 (m, 3H), 3.78 (s, 3H), 3.74 (s, 3H), 1.47 (d, J=7.3 Hz, 3H). MS 352.3 found 352.8 (M+H+) required.

Workup

extractionextracted with ethyl acetate (3×75 mL)
dry with materialThe combined organic layers were dried with Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude residue was purified by flash column chromatography (SiO2 0-40% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record: ord-5e96a03419984d22ad479602389db338
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608739B2

Reaction notes

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