Sulfuric Acid → HCID 44546741, compound

HRID 1967440Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][N:6]([CH3:20])[CH2:7][CH:8]([C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=1)O.S(=O)(=O)(O)O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:21]([CH:8]([C:10]3[CH:19]=[CH:18][C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH:11]=3)[CH2:7][N:6]([CH3:20])[CH2:5]2)=[CH:22][CH:23]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of Compound 16 (˜110 mmol) in methylene chloride (1.0 L) was added concentrated sulfuric acid (30.0 mL, 0.56 mol) and the mixture was stirred at 0° C. for 3 h. The reaction was quenched by adding 6 N NaOH until the pH was ˜9, and the aqueous phase was extracted with additional methylene chloride (3×). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (9:1 to 8:1 hexanes/ethyl acetate) to afford Compound 17 (15.79 g, 41% over 3 steps) as a white solid: 1H NMR (500 MHz, CDCl3) δ 7.82-7.70 (m, 3H), 7.66 (s, 1H), 7.49-7.41 (m, 2H), 7.28-7.20 (m, 2H), 7.16 (dd, J=8.3, 2.3 Hz, 1H), 6.75 (d, J=8.5 Hz, 1H), 4.37 (dd, J=7.5, 6.5 Hz, 1H), 3.75 (d, J=15.3 Hz, 1H), 3.62 (d, J=15.3 Hz, 1H), 3.08 (ddd, J=11.5, 6.0, 1.0 Hz, 1H), 2.64 (dd, J=11.5, 8.5 Hz, 1H), 2.43 (s, 3H). The undesired 5-bromo isomer was also obtained (11.91 g, 30% over 3 steps).

Workup

customThe reaction was quenched
additionby adding 6 N NaOH until the pH was ˜9
extractionthe aqueous phase was extracted with additional methylene chloride (3×)
dry with materialThe combined organic extracts were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography (9:1 to 8:1 hexanes/ethyl acetate)

Sources & evidence

ORD record: ord-240c97ddf7cf4f339ce9e090cf7f75f5
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420811B2

Reaction notes

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