Ammonium Chloride → HCID 59553765, compound

HRID 1170940Notes

Reaction equation

HRID 1170940 reaction equation
[C:1]1([CH2:7][CH2:8][Mg]Cl)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:16]#[N:17].N[C@H:24]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:25]([NH:27][CH3:28])=[O:26].[BH4-].[Na+].[Cl-].[NH4+]>C1COCC1.CO>[CH3:11][O:12][C:13]1[CH:14]=[C:15]([C@H:16]([NH:17][C@H:24]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:25]([NH:27][CH3:28])=[O:26])[CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:18]=[CH:19][C:20]=1[O:21][CH3:22]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 748423,4-DimethoxybenzonitrileHCID 4311764Sodium borohydrideHCID 28211238HCID 28211238, compoundHCID 178418865HCID 178418865, compound

Product 1

HCID 59553765HCID 59553765, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-phenylethylmagnesium chloride (1 M in THF, 3.0 mL, 3.00 mmol) in THF (5 mL) was added dropwise a solution of 3,4-dimethoxybenzonitrile (326 mg, 2.00 mmol) in THF (5 mL). After 23 h of reflux, dry methanol (2.5 mL) and a solution of (R)-2-amino-N-methyl-2-phenyl acetamide (accessable via: J. Org. Chem. 2005, 70, 10792-10802, 672 mg, 4.00 mmol) in dry methanol (2.5 mL) were added successively at 0° C. After stirring at ambient temperature for 1 h the reaction mixture was cooled to 0° C. and sodium borohydride (158 mg, 4.00 mmol) was added in small portions. After stirring for 5.5 h at ambient temperature, aqueous ammonium chloride (sat.) was added and extracted with tert-butylmethylether. The organic layers were combined, dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate:methanol=3:1:0 to 0:9:1) afforded the title compounds (R)-2-[(R)-1-(3,4-dimethoxy-phenyl)-3-phenyl-propylamino]-N-methyl-2-phenyl-acetamide (1st eluting compound, 175 mg, 21%) as a light yellow oil (MS: m/e=419.3 [M+H]+ and (R)-2-[(S)-1-(3,4-dimethoxy-phenyl)-3-phenyl-propylamino]-N-methyl-2-phenyl-acetamide (2nd eluting compound, 175 mg, 21%) as a light yellow oil (MS: m/e=419.3 [M+H]+.

Workup

  1. temperatureAfter 23 h of reflux
  2. temperaturewas cooled to 0° C.
  3. stirringAfter stirring for 5.5 h at ambient temperature
  4. extractionextracted with tert-butylmethylether
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customPurification by chromatography (SiO2, heptane:ethyl acetate:methanol=3:1:0 to 0:9:1)

Sources & evidence

ORD record
ord-826ade34d918440c8878837a31bca5a7
Source dataset
uspto-grants-2010_11
Patent number
US07829563B2

Reaction notes

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