Benzyl Bromide → methyl N-benzyl-N-(3-chloro-4-fluorophenyl)alaninate

HRID 1822175Notes

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].[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[I-].C([NH3+])(C)(C)C.[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[CH2:16]([N:9]([C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)[C@H:10]([C:12]([O:14][CH3:15])=[O:13])[CH3:11])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Methyl N-(3-chloro-4-fluorophenyl)alaninate (1-3, 0.740 g, 3.194 mmol) was treated with benzyl bromide (0.955 mL, 7.986 mmol) and tertbutylammonium iodide (0.118 g, 0.319 mmol) at 25° C. in DMF (100 mL) then allowed to stir 15 min. NaH was added (0.100 g, 4.153 mmol) and the resulting suspension was warmed at 50° C. while stirring over 48 h. Upon completion, the reaction was diluted with EtOAc (100 mL) and washed with NaHCO3 (sat. aq) (3×75 mL). The organic fractions were dried over sodium Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash column chromotography (SiO2, 0-40% EtOAc/hexanes gradient) to give methyl N-benzyl-N-(3-chloro-4-fluorophenyl)alaninate (2-1). 1H NMR (300 MHz, CDCl3) δ 7.31 (m, 5H), 6.91 (t, J=8.8 Hz, 1H), 6.73 (m, 1H), 6.49 (m, 1H), 4.47 (m, 3H), 3.73 (s, 3H), 1.22 (d, J=6.0 Hz, 3H). MS 322.3 found, 322.8 (M+H+) required.

Workup

stirringwhile stirring over 48 h
washwashed with NaHCO3 (sat. aq) (3×75 mL)
dry with materialThe organic fractions were dried over sodium Na2SO4
filtrationfiltered
concentrationconcentrated under vacuum
customThe residue was purified by flash column chromotography (SiO2, 0-40% EtOAc/hexanes gradient)

Sources & evidence

ORD record: ord-c959e9a02f664502bab58a22c5470311
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608739B2

Reaction notes

Loading…