Butylamine → Phenylmethyl 4-bromo-2-(butylamino)benzoate

HRID 47691Notes

Reaction equation

[Br:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[C:4](F)[CH:3]=1.[CH2:19]([NH2:23])[CH2:20][CH2:21][CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[Br:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[C:4]([NH:23][CH2:19][CH2:20][CH2:21][CH3:22])[CH:3]=1

Participants

Conditions

Temperature: 75 °C

Procedure

Phenylmethyl 4-bromo-2-fluorobenzoate (Example 192, 315 mg, 1.02 mmol) was combined with n-butylamine (110 μl, 1.12 mmol, 1.1 eq.) and solid cesium carbonate (1.66 g, 5.1 mmol, 5.0 eq.) in anhydrous methyl sulfoxide (4 mL) and heated at 75° C. for 1.5 hours. The reaction was cooled and partitioned between diethyl ether and water. The aqueous layer was separated and extracted with fresh ether. The organic layers were combined, washed with brine (4×), dried (MgSO4), and concentrated in vacuo to a crude oil. The crude was purified by flash chromatography on silica gel eluted with 95:5 hexanes/ether to provide the title compound as a yellow oil (52 mg, 14%): 1H NMR (300 MHz, CDCl3) δ7.76 (d, 1 H), 7.71 (broad s, 1 H), 7.41-7.32 (m, 5 H), 6.80 (s, 1 H), 6.63 (d, 1 H), 5.26 (s, 2 H), 3.16-3.10 (m, 2 H), 1.69-1.60 (m, 2 H), 150-1.38 (m, 2 H), 0.95 (t, 3 H); MS m/z 362.0 and 364.0 (MH+ and MH+2).

Workup

temperatureThe reaction was cooled
custompartitioned between diethyl ether and water
customThe aqueous layer was separated
extractionextracted with fresh ether
washwashed with brine (4×)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo to a crude oil
customThe crude was purified by flash chromatography on silica gel
washeluted with 95:5 hexanes/ether

Sources & evidence

ORD record: ord-49214b56bc764f3f80d5d1f43fc47303
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06699860B2

Reaction notes

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