Diisopropylethylamine → Methyl 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzoate

HRID 541347Notes

Reaction equation

HRID 541347 reaction equation
[CH:1]1([C:5]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:8]([C:9](O)=[O:10])=[C:7]([CH2:18][CH3:19])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.Cl.[NH:21]1[CH2:26][CH2:25][CH:24]([C:27]2[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O>[C:31]([C:30]1[CH:33]=[CH:34][C:27]([CH:24]2[CH2:25][CH2:26][N:21]([C:9]([C:8]3[C:7]([CH2:18][CH3:19])=[CH:6][C:5]([CH:1]4[CH2:4][CH2:3][CH2:2]4)=[C:13]([CH:12]=3)[C:14]([O:16][CH3:17])=[O:15])=[O:10])[CH2:22][CH2:23]2)=[CH:28][CH:29]=1)#[N:32]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 682889334-Cyclobutyl-2-ethyl-5-(methoxycarbonyl)benzoic acid2×

Product 1

HCID 68288508Methyl 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzoateYield 95.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a round-bottom flask were added a solution of 4-cyclobutyl-2-ethyl-5-(methoxycarbonyl)benzoic acid (compound 215.4, 1.15 g, 4.38 mmol, 1.00 equiv), 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 1.07 g, 4.80 mmol, 1.10 equiv), HBTU (2.50 g, 6.59 mmol, 1.50 equiv), and DIEA (1.07 g, 8.28 mmol, 3.00 equiv) in N,N-dimethylformamide (10 mL). The resulting solution was stirred for 1 h at 25° C. The reaction was then quenched by the addition of 20 mL of water. The resulting mixture was extracted with 2×50 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:3) to yield 1.80 g (95%) of methyl 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzoate as a yellow solid.

Workup

  1. customThe reaction was then quenched by the addition of 20 mL of water
  2. extractionThe resulting mixture was extracted with 2×50 mL of ethyl acetate
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified

Sources & evidence

ORD record
ord-3315e1519fa04b4f930ef7c132551e8e
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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