Hydrochloric Acid → (2-(4-Bromo-2-fluoro-benzylcarbamoyl)-4-nitro-phenoxy]-acetic acid tert-butyl ester

HRID 457945Notes

Reaction equation

[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8](=[O:19])[C:9]2[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=2[OH:18])=[C:4]([F:22])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].Cl>CC(C)=O>[C:34]([O:33][C:31](=[O:32])[CH2:30][O:18][C:10]1[CH:11]=[CH:12][C:13]([N+:15]([O-:17])=[O:16])=[CH:14][C:9]=1[C:8](=[O:19])[NH:7][CH2:6][C:5]1[CH:20]=[CH:21][C:2]([Br:1])=[CH:3][C:4]=1[F:22])([CH3:37])([CH3:36])[CH3:35]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of N-(4-bromo-2-fluoro-benzyl)-2-hydroxy-5-nitro-benzamide (0.95 g, 2.6 mmol) in acetone (15 mL, 0.2 M) was treated with aq K2CO3 (2 M, 1.9 mL, 3.8 mmol) and t-butyl bromoacetate (2.2 mL, 8.4 mmol). After heating to 50° C. for 30 h, the reaction was acidified to pH 1–2 with 2 N HCl and extracted with ethyl acetate (3×). The combined organic extracts were washed With saturated aq NaCl, dried over Na2SO4, filtered and concentrated. The crude oil was crystallized from heptane and ethyl acetate to give [2-(4-bromo-2-fluoro-benzylcarbamoyl)-4-nitro-phenoxy]-acetic acid tert-butyl ester as a white crystalline solid (1.21 g, 97%): 1H NMR (DMSO-d6, 300 MHz) δ 9.01 (br t, J=5.7 Hz, 1 H), 8.58 (d, J=3.0 Hz, 1 H), 8.33 (dd, J1=9.0 Hz, J2=3.0 Hz, 1 H), 7.51 (br d, J=9.6 Hz, 1 H), 7.42–7.34 (m, 2 H)., 7.32 (d, J=9.3 Hz, 1 H), 4.99 (s, 2 H), 4.52 (d, J=5.7 Hz, 2 H), 1.40 (s, 9 H).

Workup

extractionextracted with ethyl acetate (3×)
washThe combined organic extracts were washed With saturated aq NaCl
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude oil was crystallized from heptane and ethyl acetate

Sources & evidence

ORD record: ord-7450b62e03d04d01ad6e9055d04f4044
Source dataset: uspto-grants-2007_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07189749B2

Reaction notes

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