5-Bromo-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile → Ethyl 4-(2-((4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl)(methyl)amino)ethyl)benzoate

HRID 587943Notes

Reaction equation

HRID 587943 reaction equation
Br[CH2:2][CH2:3][CH2:4][C:5]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)([CH:8]([CH3:10])[CH3:9])[C:6]#[N:7].[CH3:21][NH:22][CH2:23][CH2:24][C:25]1[CH:35]=[CH:34][C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:27][CH:26]=1>C1COCC1>[C:6]([C:5]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:3][CH2:2][N:22]([CH3:21])[CH2:23][CH2:24][C:25]1[CH:35]=[CH:34][C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:27][CH:26]=1)#[N:7]

Participants

4

Reactant 2

HCID 135355715-Bromo-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrileHCID 59419931Ethyl 4-(2-(methylamino)ethyl)benzoate

Product 1

HCID 25108828Ethyl 4-(2-((4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl)(methyl)amino)ethyl)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
90 °C

Procedure

A solution of 0.326 g (0.961 mmol) of 1f in 1 mL of THF and a separate solution of 0.292 g (1.41 mmol) of 2c in 1 mL of THF were combined. The resulting solution was heated in a 90° C. oil bath and the THF was evaporated under a slow stream of nitrogen. The resulting mixture was stirred under nitrogen at 85° C. for 18 h, cooled to 22° C. and partitioned between saturated NaHCO3 and ethyl acetate. The organic layer was dried (Na2SO4) and evaporated and the residue purified by flash chromatography on silica gel, eluting first with DCM and then gradually increasing to 2% methanol/DCM to give 3r as a colorless oil; MS found M+H=467. The oxalate salt of 3r was recrystallized from ethyl acetate; mp 111-112° C.

Workup

  1. customthe THF was evaporated under a slow stream of nitrogen
  2. temperaturecooled to 22° C.
  3. custompartitioned between saturated NaHCO3 and ethyl acetate
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customevaporated
  6. customthe residue purified by flash chromatography on silica gel
  7. washeluting first with DCM
  8. temperaturegradually increasing to 2% methanol/DCM

Sources & evidence

ORD record
ord-6ce7d2ecd2fa4f29a1759d7de71ee274
Source dataset
uspto-grants-2016_01
Patent number
US09227918B2

Reaction notes

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