Ammonium Chloride → Tert-butyl 4-(4-methoxy-3-methylbenzoyl)piperidine-1-carboxylate

HRID 1752235Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1752235
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:19])N(OC)C)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([Mg]Br)=[CH:24][C:23]=1[CH3:30].[NH4+].[Cl-]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:19])[C:25]2[CH:26]=[CH:27][C:22]([O:21][CH3:20])=[C:23]([CH3:30])[CH:24]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

5

Edukt 3

HCID 25517Ammonium ChlorideHCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 178491913HCID 178491913, Verbindung

Produkt 1

HCID 71212195Tert-butyl 4-(4-methoxy-3-methylbenzoyl)piperidine-1-carboxylateAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A stirred solution of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (3.0 g, 11.02 mmol) in 30 mL THF was cooled to 0° C., then (4-methoxy-3-methylphenyl)magnesium bromide (6.21 g, 27.5 mmol) was added dropwise via a syringe under N2 and the reaction mixture was stirred at the same temperature for 1.5 h, then gradually warmed up to room temperature over 1 h when the reaction was judged complete by LCMS. To the reaction mixture was slowly added 40 mL of saturated aqueous NH4Cl then the aqueous solution was extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine, dried over Na2SO4 and the solvent was removed to yield the crude product. Purification by flash chromatography gave the title compound as a white solid (1.97 g, 5.62 mmol, 51% yield). MS (ESI) m/z 334.4 (M+H+); HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 35-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) retention time=1.57 min. 1H NMR (400 MHz, CDCL3) 8 ppm 1.48 (s, 9H) 1.62-1.91 (m, 4H) 2.27 (s, 3H) 2.78-3.02 (m, 2H) 3.27-3.46 (m, 1H) 3.91 (s, 3H) 4.12-4.27 (m, 2H) 6.87 (d, J=8.59 Hz, 1H) 7.77 (t, J=8.10 Hz, 2H).

Aufarbeitung

  1. extractionthe aqueous solution was extracted with ethyl acetate (2×50 mL)
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed
  5. customto yield the crude product
  6. customPurification by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-5b90be8a31ef49b09585c4859d06e48c
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09163003B2

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