Hydrochloric Acid → (2-Aminophenyl)(3-methoxyphenyl)methanone

HRID 1870732Notes

Reaction equation

CON(C)[C:4](=[O:13])[C:5]1[C:6](=[CH:8][C:9](Cl)=[CH:10][CH:11]=1)[NH2:7].Br[C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1N)[O:19][CH3:20].[Li]CCCC.Cl>C1COCC1>[NH2:7][C:6]1[CH:8]=[CH:9][CH:10]=[CH:11][C:5]=1[C:4]([C:16]1[CH:23]=[CH:22][CH:21]=[C:18]([O:19][CH3:20])[CH:17]=1)=[O:13]

Participants

Conditions

Temperature: -78 °C

Procedure

In a flame-dried round bottom flask 4-chloroanthranilic acid N-methoxy-N-methylamide (4.58 g, 21.3 mmol) and m-bromoanisidine (4.02 g, 21.5 g) were dissolved in THF (185 mL) and the resulting solution was cooled to -78° C. With vigorous stirring, 2 equiv of nBuLi in hexanes (26.9 mL, 1.6 M, 43.0 mmol) was added dropwise by a syringe pump at 0.6 mL/min. After 20 min, 40 mL of 1 N hydrochloric acid was carefully added, the mixture was extracted with ethyl acetate (300 mL), and the ethyl acetate was washed with water (100 mL) and brine (100 mL), dried over sodium sulfate and concentrated in vacuo. Flash chromatography with hexanes/ethyl acetate (95:5, then 75:25) afforded 3.75 g (67% yield) of 2-amino-3'-methoxybenzophenone as a yellow oil. 1H NMR (50 MHz, CDCL3): δ 3.83 (s, 3), 6.17 (b, 2), 6.55 (dd, 1, J=2.0, 8.5), 6.72 (d, 1, J=2.0), 7.06 (dd, 1, J=2.6, 8.5), 7.13 (m, 2), 7.35 (t, 1, J=7.8), 7.39 (d, 1, J=8.5). 2-Amino-4-chloro-3'-methoxybenzophenone was converted to 2-amino-4-chloro-3'-hydroxybenzophenone (below) prior to full characterization.

Workup

extractionthe mixture was extracted with ethyl acetate (300 mL)
washthe ethyl acetate was washed with water (100 mL) and brine (100 mL)
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-8abb4622bc80471ca3867734737a66e8
Source dataset: uspto-grants-2000_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06100254

Reaction notes

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