Sodium Dithionite → 4-Phenylethynyl-N2-(1-(R)-methyl-2,2-dimethylpropyl)benzene-1,2-diamine

HRID 250750Notes

Reaction equation

HRID 250750 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]#[C:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][C:5]=1[NH:18][C@H:19]([CH3:24])[C:20]([CH3:23])([CH3:22])[CH3:21])([O-])=O.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C1COCC1.O.[OH-].[NH4+].C(OCC)(=O)C>[C:12]1([C:11]#[C:10][C:7]2[CH:6]=[C:5]([NH:18][C@H:19]([CH3:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[C:4]([NH2:1])=[CH:9][CH:8]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 2

HCID 24489Sodium DithioniteHCID 66868959(2-nitro-5-phenylethynylphenyl)-(1-(R)-methyl-2,2-dimethylpropyl)amine

Product 1

HCID 668692274-Phenylethynyl-N2-(1-(R)-methyl-2,2-dimethylpropyl)benzene-1,2-diamineYield 75%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Procedure

Stir (5-Chloro-2-nitrophenyl)-(1-(R)-methyl-2,2-dimethylpropyl)amine (17.23 g, 0.067 mol), copper (I) iodide (0.64 g, 0.0034 mol), (oxydi-2,1-phenylene)bis(diphenylphosphine) (3.61 g, 0.0067 mol), phenylacetylene (12.5 mL, 0.114 mol) in DMF (200 mL) and diethylamine (50 mL) for 5 minutes. Add palladium (II) acetate (0.753 g, 0.0034 mol) and heat to 95° C. for 4 h. Cool to ambient temperature and evaporate off diethylamine under reduced pressure and pour into hexane. Filter insolubles and evaporate off hexane. Dilute with ethyl ether (1 L), filter and wash filtrate with water (2×1 L), saturated sodium chloride, dry magnesium sulfate, concentrate and purify (silica gel chromatography eluting with hexane/dichloromethane mixtures) to give 27.9 g of crude (2-nitro-5-phenylethynylphenyl)-(1-(R)-methyl-2,2-dimethylpropyl)amine that was used in the next step without further purification. To a solution of impure (2-nitro-5-phenylethynylphenyl)-(1-(R)-methyl-2,2-dimethylpropyl)amine (27.9 g) in THF (350 mL), water (100 mL), concentrated ammonium hydroxide (150 mL), Na2S2O4 (73.6 g, 0.423 mol) and stir for about 18 hours. Dilute with ethyl acetate and wash with saturated sodium chloride, dry with magnesium sulfate, concentrate and purify (silica gel chromatography with hexane/dichloromethane mixtures to give 14.51 g of the desired compound (75% for 2 Steps).

Workup

  1. customwas used in the next step without further purification
  2. washwash with saturated sodium chloride
  3. dry with materialdry with magnesium sulfate
  4. concentrationconcentrate
  5. custompurify (silica gel chromatography with hexane/dichloromethane

Sources & evidence

ORD record
ord-b0a9acdc8b8040898f203c171a9f8ba3
Source dataset
uspto-grants-2011_01
Patent number
US07863310B2

Reaction notes

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