Cesium carbonate → methyl 4-(4-(N-(2,4-dimethylphenyl)-N-isobutylsulfamoyl)phenyl)-4-nitrobutanoate

HRID 1487058Notes

Reaction equation

HRID 1487058 reaction equation
[N+:1]([CH2:4][CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8])([O-:3])=[O:2].Br[C:12]1[CH:17]=[CH:16][C:15]([S:18]([N:21]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[CH3:33])[CH2:22][CH:23]([CH3:25])[CH3:24])(=[O:20])=[O:19])=[CH:14][CH:13]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH3:33][C:27]1[CH:28]=[C:29]([CH3:32])[CH:30]=[CH:31][C:26]=1[N:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[S:18]([C:15]1[CH:14]=[CH:13][C:12]([CH:4]([N+:1]([O-:3])=[O:2])[CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8])=[CH:17][CH:16]=1)(=[O:20])=[O:19]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 25604Methyl 4-nitrobutyrateHCID 27349372-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylHCID 867315904-bromo-N-(2,4-dimethylphenyl)-N-isobutylbenzenesulfonamide

Product 1

HCID 89479545methyl 4-(4-(N-(2,4-dimethylphenyl)-N-isobutylsulfamoyl)phenyl)-4-nitrobutanoate

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 4-nitrobutanoate (0.094 mL, 0.757 mmol), 4-bromo-N-(2,4-dimethylphenyl)-N-isobutylbenzenesulfonamide (200 mg, 0.505 mmol), di-tert-butyl(2′-methyl-[1,1′-biphenyl]-2-yl)phosphine (15.77 mg, 0.050 mmol) and cesium carbonate (197 mg, 0.606 mmol) in 1,2-dimethoxyethane (DME) (3 mL) at room temperature was added bis(dibenzylideneacetone)palladium(0) (14.51 mg, 0.025 mmol). The vial was flushed with nitrogen for 2 minutes then sealed and heated by microwaves (Emrys Optimiser) to 120° C. for 60 minutes. The reaction mixture was cooled then passed through a pre-packed silica (Si) cartridge, eluting with methanol (15 mL). The resulting filtrate was evaporated in vacuo then purified by mass directed autoprep (formic acid modifier). The relevant fractions were concentrated under a stream of nitrogen to give the required product (N70% pure), 96 mg, used directly in next step without further purification. LCMS [LCMS1] Rt 1.41 min, m/z (ES+) 463 (M+H).

Workup

  1. customThe vial was flushed with nitrogen for 2 minutes
  2. customthen sealed
  3. temperatureThe reaction mixture was cooled
  4. washeluting with methanol (15 mL)
  5. customThe resulting filtrate was evaporated in vacuo
  6. customthen purified by mass
  7. concentrationThe relevant fractions were concentrated under a stream of nitrogen

Sources & evidence

ORD record
ord-29afcec7b0614ab4b19ec366d793f777
Source dataset
uspto-grants-2016_08
Patent number
US09428452B2

Reaction notes

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