Diisopropylethylamine → 4-(1-(3-Formyl-4-methylbenzoyl)piperidin-4-yl)benzonitrile

HRID 541212Notes

Reaction equation

HRID 541212 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:6]([OH:8])=O)=[O:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH:38]1[CH2:43][CH2:42][CH:41]([C:44]2[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[CH:46][CH:45]=2)[CH2:40][CH2:39]1.CCN(C(C)C)C(C)C>CN(C)C=O.CCOC(C)=O>[CH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:6]([N:38]1[CH2:43][CH2:42][CH:41]([C:44]2[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[CH:46][CH:45]=2)[CH2:40][CH2:39]1)=[O:8])=[O:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 190191913-Formyl-4-methylbenzoic acid2×HCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)

Product 1

HCID 866725244-(1-(3-Formyl-4-methylbenzoyl)piperidin-4-yl)benzonitrileYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-formyl-4-methylbenzoic acid (compound 39.1, 660 mg, 4.02 mmol, 1.00 equiv), HBTU (2 g, 5.28 mmol, 1.30 equiv) in N,N-dimethylformamide (20 mL) was stiffed at room temperature. After 1 h, 4-(piperidin-4-yl)benzonitrile hydrochloride (1.5, 890 mg, 4.01 mmol, 1.00 equiv) and DIEA (1.03 g, 7.98 mmol, 2.00 equiv) were added. The resulting mixture was stirred for 5 h at room temperature and then overnight at 60° C. in. After cooling to ambient temperature, the reaction mixture was diluted with 100 mL of EtOAc and washed with 2×50 mL of NH4Cl (aq., sat.) followed by 2×50 mL of sodium bicarbonate (aq., sat.). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield 1 g (75%) of the title compound as a brown oil.

Workup

  1. customwas stiffed at room temperature
  2. customovernight
  3. customat 60° C.
  4. temperatureAfter cooling to ambient temperature
  5. washwashed with 2×50 mL of NH4Cl (aq., sat.)
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2ea350849677405c868ee2f4ab50cdf8
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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