Ethyl Acetate → 4'-(2-carboxy-2-methylpropyl)-N-(isobutoxycarbonyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamide

HRID 1378360Notes

Reaction equation

HRID 1378360 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].I[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S:14]([N:17]([C:27]([O:29][CH2:30][CH:31]([CH3:33])[CH3:32])=[O:28])[C:18]1[C:23]([O:24][CH3:25])=[N:22][C:21]([CH3:26])=[CH:20][N:19]=1)(=[O:16])=[O:15].[C:34]([C:37]([CH3:49])([CH3:48])[CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O)([OH:36])=[O:35].C(OCC)(=O)C>O.C1(C)C=CC=CC=1.C(O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[C:34]([C:37]([CH3:49])([CH3:48])[CH2:38][C:39]1[CH:44]=[CH:43][C:42]([C:8]2[C:9]([S:14]([N:17]([C:27]([O:29][CH2:30][CH:31]([CH3:33])[CH3:32])=[O:28])[C:18]3[C:23]([O:24][CH3:25])=[N:22][C:21]([CH3:26])=[CH:20][N:19]=3)(=[O:16])=[O:15])=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:41][CH:40]=1)([OH:36])=[O:35]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 18704832N-(isobutoxycarbonyl)-N-(3-methoxy-5-methyl-2-pyrazinyl)-2-iodobenzenesulphonamideHCID 21186352(2-Carboxy-2-methylpropyl)benzeneboronic acid

Product 1

HCID 229112884'-(2-carboxy-2-methylpropyl)-N-(isobutoxycarbonyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamideYield 33%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

A solution of sodium carbonate (2.86 g) in water (4 ml) was added to a soultion of 2-iodo- N-(isobutoxycarbonyl)- N-(3-methoxy-5-methylpyrazin-2-yl)benzenesulphonamide (6.2 g), (2-carboxy-2-methylpropyl)benzeneboronic acid (3.0 g) and tetrakis(triphenylphosphine)palladium(O) (235 mg) in toluene (30 ml) and ethanol (20 ml). The mixture was stirred vigorously and heated under reflux for 18 hours under an atmosphere of argon. Water (100 ml) and ethyl acetate (100 ml) were added and the organic layer was separated. The organic phase was extracted with saturated sodium bicarbonate solution (50 ml) and the aqueous phases were combined. The solution was acidifed with 6M hydrochloric acid and extracted with ethyl acetate (3×50 ml). The extracts were washed with water (50 ml) and saturated sodium chloride solution (50 ml) and then dried (MgSO4). Volatile material was removed by evaporation and the residue was triturated with etherexane (1:1 v/v) to give 4'-(2-carboxy-2-methylpropyl)- N-(isobutoxycarbonyl)- N-(3-methoxy-5 -methylpyrazin-2-yl)-2-biphenylsulphonamide (2.25 g); 1H NMR (d6 -DMSO): 0.6 (d, 6H), 1.1 (s, 6H), 1.5-1.7 (m, 1H), 2.52 (s, 3H), 2.85 (s, 2H), 3.8 (d, 2H), 3.95 (s, 3H), 7.15 (d, 2H), 7.25 (d, 2H), 7.3-7.4 (m, 1H), 7.7-7.8 (m, 2H), 8.15 (s, 1H), 8.5-8.6 (m, 1H), 12.3 (s, 1H).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 18 hours under an atmosphere of argon
  3. customthe organic layer was separated
  4. extractionThe organic phase was extracted with saturated sodium bicarbonate solution (50 ml)
  5. extractionextracted with ethyl acetate (3×50 ml)
  6. washThe extracts were washed with water (50 ml) and saturated sodium chloride solution (50 ml)
  7. dry with materialdried (MgSO4)
  8. customVolatile material was removed by evaporation
  9. customthe residue was triturated with etherexane (1:1 v/v)

Sources & evidence

ORD record
ord-8cb2528eb8ff4ceb932cafccadbe0826
Source dataset
uspto-grants-1997_09
Patent number
US05668137

Reaction notes

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