1-Bromo-4-(2-methylpropoxy)benzene → 2-Chloro-5-(4-isobutoxy-benzoyl)-benzenesulfonamide

HRID 1515444Notes

Reaction equation

HRID 1515444 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]([CH3:12])[CH3:11])=[CH:4][CH:3]=1.C([Li])CCC.[Cl:18][C:19]1[CH:30]=[CH:29][C:22]([C:23](N(OC)C)=[O:24])=[CH:21][C:20]=1[S:31](=[O:34])(=[O:33])[NH2:32]>O1CCCC1>[Cl:18][C:19]1[CH:30]=[CH:29][C:22]([C:23](=[O:24])[C:2]2[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]([CH3:12])[CH3:11])=[CH:4][CH:3]=2)=[CH:21][C:20]=1[S:31]([NH2:32])(=[O:34])=[O:33]

Participants

5

Reactant 3

HCID 153241111-Bromo-4-(2-methylpropoxy)benzeneHCID 581073994-chloro-N-methoxy-N-methyl-3-sulfamoyl-benzamideHCID 178418339Butyllithium

Product 1

HCID 442357412-Chloro-5-(4-isobutoxy-benzoyl)-benzenesulfonamideYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

1-Bromo-4-isobutoxy-benzene (625 mg, 2.73 mmol) is dissolved in tetrahydrofuran (2 mL) and cooled to −78° C. The solution is treated with a solution of n-butyllithium (1.6 M in hexanes, 1.7 mL, 2.73 mmol) and stirred 30 minutes after which a solution of 4-chloro-N-methoxy-N-methyl-3-sulfamoyl-benzamide (250 mg, 0.91 mmol) in tetrahydrofuran (2 mL) is added. The reaction is allowed to stir for 18 hours while warming to ambient temperature. The reaction is quenched with a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic phase is separated and concentrated in vacuo. The residue is purified by column chromatography (gradient of ethyl acetate in hexanes 10-50%) affording 120 mg (37% yield) of the title compound. 1H NMR (DMSO) δ 1.00 (d, 6H, J=6.56 Hz), 2.01-2.10 (m, 1H), 3.88 (d, 2H, J=6.57 Hz), 7.11 (d, 2H, J=8.85 Hz), 7.76 (d, 2H, J=8.85 Hz), 7.81-7.84 (m, 3H), 7.89 (dd, 1H, J=2.02, 8.08), 8.24 (d, 1H, J=2.02). MS (m/z): 366 (M−1). CHN Calc C, 55.51; H, 4.93; N, 3.81. Found C, 55.38; H, 4.74; N, 3.77.

Workup

  1. additionis added
  2. temperaturewhile warming to ambient temperature
  3. customThe reaction is quenched with a saturated solution of ammonium chloride
  4. extractionextracted with ethyl acetate
  5. customThe organic phase is separated
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by column chromatography (gradient of ethyl acetate in hexanes 10-50%)

Sources & evidence

ORD record
ord-d839b5b5ce6348b3a0f0c298e5484124
Source dataset
uspto-grants-2012_07
Patent number
US08222424B2

Reaction notes

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