Diisopropylethylamine → Methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate

HRID 541372Notes

Reaction equation

HRID 541372 reaction equation
[CH:1]1([C:4]2[C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([CH2:17][CH3:18])[CH:5]=2)[CH2:3][CH2:2]1.Cl.[F:20][C:21]1([C:27]2[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=2)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[C:31]([C:30]1[CH:29]=[CH:28][C:27]([C:21]2([F:20])[CH2:26][CH2:25][N:24]([C:8]([C:7]3[C:6]([CH2:17][CH3:18])=[CH:5][C:4]([CH:1]4[CH2:2][CH2:3]4)=[C:12]([CH:11]=3)[C:13]([O:15][CH3:16])=[O:14])=[O:10])[CH2:23][CH2:22]2)=[CH:34][CH:33]=1)#[N:32]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682881524-Cyclopropyl-2-ethyl-5-(methoxycarbonyl)benzoic acid2×HCID 682888554-(4-Fluoropiperidin-4-yl)benzonitrile hydrochloride2×

Product 1

HCID 68288315Methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-cyclopropyl-2-ethyl-5-(methoxycarbonyl)benzoic acid (compound 226.6, 150 mg, 0.600 mmol, 1.00 equiv) in N,N-dimethylformamide (15 mL) were added 4-(4-fluoropiperidin-4-yl)benzonitrile hydrochloride (compound 11.2, 150 mg, 0.620 mmol, 1.00 equiv), DIPEA (450 mg, 3.49 mmol, 6.00 equiv), and HBTU (300 mg, 0.790 mmol, 1.30 equiv). The resulting solution was stirred for 4 h at 20° C., then quenched by the addition of 20 mL of brine. The resulting mixture was extracted with 4×30 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified via silica gel column with ethyl acetate/petroleum ether (1:3) as eluent. This resulted in 0.200 g (76%) of methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate as a light yellow solid.

Workup

  1. customquenched by the addition of 20 mL of brine
  2. extractionThe resulting mixture was extracted with 4×30 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 via silica gel column with ethyl acetate/petroleum ether (1:3) as eluent
  6. customThis resulted in 0.200 g (76%) of methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate as a light yellow solid

Sources & evidence

ORD record
ord-f67335224c804b9eb9ba54a90ca90655
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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