Diisopropylethylamine → N-(8-methoxytetralin-2-yl)-N-propyl-2-(2,5-dimethylphenyl)acetamide

HRID 2362599Notes

Reaction equation

HRID 2362599 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][C:10]([OH:12])=O.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[CH3:46][O:47][C:48]1[CH:49]=[CH:50][CH:51]=[C:52]2[C:57]=1[CH2:56][CH:55]([NH:58][CH2:59][CH2:60][CH3:61])[CH2:54][CH2:53]2>CN(C=O)C>[CH3:46][O:47][C:48]1[CH:49]=[CH:50][CH:51]=[C:52]2[C:57]=1[CH2:56][CH:55]([N:58]([CH2:59][CH2:60][CH3:61])[C:10](=[O:12])[CH2:9][C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[CH3:1])[CH2:54][CH2:53]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 836152,5-Dimethylphenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 127414178-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine

Product 1

HCID 67250560N-(8-methoxytetralin-2-yl)-N-propyl-2-(2,5-dimethylphenyl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A mixture of 340 mg (2.1 mmol) 2,5-dimethylphenylacetic acid (A3-4: W=OH, Cy=2,5-dimethylphenyl) and 0.70 mL diisopropylethylamine (DIPEA) (4.24 mmol) in 10 mL of dry DMF was cooled in an ice-bath. After addition of 950 mg (2.5 mmol) O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) in 5.0 mL dry DMF a solution of 640 mg (2.9 mmol) of the free base of N-(8-methoxytetralin-2-yl)-N-propylamine (A2-1) in 8.0 mL dry DMF was added dropwise, the ice-bath was removed and the reaction mixture was stirred for 3 hrs at room temperature. The mixture was washed with a saturated solution of aqueous NaHCO3 for several times and the resulting aqueous layer was extracted with CH2Cl2. The organic layers were dried over MgSO4 and the solvent was evaporated in vacuo. Flash chromatography of the residue on silica gel with a mixture of hexane/ethyl acetate 60/10 gave the product N-(8-methoxytetralin-2-yl)-N-propyl-2-(2,5-dimethylphenyl)acetamide.

Workup

  1. temperaturewas cooled in an ice-bath
  2. additionwas added dropwise
  3. customthe ice-bath was removed
  4. washThe mixture was washed with a saturated solution of aqueous NaHCO3 for several times
  5. extractionthe resulting aqueous layer was extracted with CH2Cl2
  6. dry with materialThe organic layers were dried over MgSO4
  7. customthe solvent was evaporated in vacuo
  8. additionFlash chromatography of the residue on silica gel with a mixture of hexane/ethyl acetate 60/10

Sources & evidence

ORD record
ord-7368ebdd03bb4827b750326a9302725f
Source dataset
uspto-grants-2014_04
Patent number
US08691839B2

Reaction notes

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