Diisopropylethylamine → 3-{1-[2-(5-Methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-benzoic acid ethyl ester

HRID 385294

Reaktionsgleichung

Reaktionsgleichung von HRID 385294
[CH3:1][C:2]1[N:6]([CH2:7][C:8]([OH:10])=O)[N:5]=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.C(N(C(C)C)CC)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.Cl.[CH2:58]([O:60][C:61](=[O:74])[C:62]1[CH:67]=[CH:66][CH:65]=[C:64]([CH:68]2[CH2:73][CH2:72][NH:71][CH2:70][CH2:69]2)[CH:63]=1)[CH3:59]>CN(C=O)C>[CH2:58]([O:60][C:61](=[O:74])[C:62]1[CH:67]=[CH:66][CH:65]=[C:64]([CH:68]2[CH2:69][CH2:70][N:71]([C:8](=[O:10])[CH2:7][N:6]3[C:2]([CH3:1])=[CH:3][C:4]([C:11]([F:14])([F:13])[F:12])=[N:5]3)[CH2:72][CH2:73]2)[CH:63]=1)[CH3:59]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 5961182-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acidHCID 66973363Ethyl 3-piperidin-4-ylbenzoate hydrochlorideHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

Produkt 1

HCID 669733443-{1-[2-(5-Methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-benzoic acid ethyl esterAusbeute 49,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of (5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid (5.23 g, 20.75 mmol) in DMF (50 mL) was added diisopropylethylamine (43 mL, 207.58 mmol), followed by 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (10.52 g, 22.83 mmol) at RT. After stirring 15 min. at RT, 3-piperidin-4-yl-benzoic acid ethyl ester hydrochloride salt (5.6 g, 20.75 mmol) was added to the reaction mixture. After stirring overnight at RT, solvent was evaporated and the resulting brown oil was dissolved in ethylacetate (200 mL), washed with aq. sat. sodium bicarbonate solution (100 mL) and the aqueous phase was re-extracted with ethylacetate (200 mL). The combined organic layers were washed with 1M HCl solution (400 mL) and brine (400 mL), dried over sodium sulfate, filtered, and evaporated under reduce pressure. The crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 0:1 to 1:1) to give 3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-benzoic acid ethyl ester (4.35 g, 49.5%). 1H-NMR (400 MHz, d6-DMSO): δ=1.28-1.39 (t, 3H), 1.45-1.55 (m, 1H), 1.65-1.1.79 (m, 1H), 1.80-1.91 (m, 2H), 2.22 (s, 3H), 2.68-2.73 (m, 1H), 2.89-2.95 (m, 1H), 3.99-4.04 (m, 1H), 4.29-4.33 (q, 2H), 4.46-4.52 (m, 1H), 5.21-5.38 (dd, 2H, diastereotopic), 6.50 (s, 1H), 7.47 (t, 1H), 7.55 (d, 1H), 7.80 (s, 1H), 7.81 (d, 1H). MS: m/z=424 (M+1).

Aufarbeitung

  1. stirringAfter stirring overnight at RT
  2. customsolvent was evaporated
  3. dissolutionthe resulting brown oil was dissolved in ethylacetate (200 mL)
  4. washwashed with aq. sat. sodium bicarbonate solution (100 mL)
  5. extractionthe aqueous phase was re-extracted with ethylacetate (200 mL)
  6. washThe combined organic layers were washed with 1M HCl solution (400 mL) and brine (400 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 0:1 to 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-c0e554e0f79946b3994a23893ca4f742
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367844B2

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