Ethyl 4-piperidinecarboxylate → Ethyl 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylate

HRID 1804828

Reaktionsgleichung

Reaktionsgleichung von HRID 1804828
CC(C)([O-])C.[Na+].Br[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[CH:9]=1.[NH:17]1[CH2:22][CH2:21][CH:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18]1>C1(C)C=CC=CC=1.CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd]>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([N:17]2[CH2:22][CH2:21][CH:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:9][C:10]=1[O:15][CH3:16]

Komponenten

6

Edukt 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 27695675-Bromo-2-chloroanisoleHCID 23676156Sodium t-butoxide

Produkt 1

HCID 68554705Ethyl 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylateAusbeute 56,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 119822622-(2'-Di-tert-butylphosphine)biphenylpalladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A 10-mL round bottom flask containing a magnetic stir bar and fitted with a condenser and a inert gas inlet was charged successively with sodium tert-butoxide (304 mg, 3.16 mmol), acetato (2′-di-t-butylphosphino-1,1′-biphenyl-2-yl) palladium (II) (20.90 mg, 0.045 mmol) and a solution of 4-bromo-1-chloro-2-methoxybenzene (500 mg, 2.258 mmol) and ethyl piperidine-4-carboxylate (426 mg, 2.71 mmol) in anhydrous toluene (2.5 mL). The flask was purged with argon and the mixture heated at 80° C. After 45 min, the reaction was cooled to RT, diluted with Et2O (50 mL) and washed with water (2×15 mL) and brine (15 mL). The organic layer was dried (MgSO4) and concentrated on a rotary evaporator to give the crude product, which was purified by flash chromatography using a 12 g silica gel cartridge and 20:1 Hex/EtOAc to 10:1 Hex/EtOAc to elute the product. The fractions containing the product were pooled and concentrated on a rotary evaporator to give ethyl 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylate (380 mg, 1.276 mmol, 56% yield) as a colorless oil. LC/MS [M+H]+=298.28. 1H-NMR (400 MHz, CDCl3) δ 7.18 (1 H, d, J=8.57 Hz), 6.50 (1 H, s), 6.44 (1 H, s), 4.15 (2H, q, J=7.10 Hz), 3.87 (3 H, s), 3.58 (2 H, dt, J=12.47, 3.65 Hz), 2.79 (2 H, s), 2.38-2.47 (1 H, m), 2.02 (2 H, d, J=11.42 Hz), 1.88 (2 H, s), 1.26 (3 H, t, J=7.14 Hz).

Aufarbeitung

  1. additionA 10-mL round bottom flask containing a magnetic stir bar
  2. customfitted with a condenser and a inert gas inlet
  3. customThe flask was purged with argon
  4. temperaturethe reaction was cooled to RT
  5. additiondiluted with Et2O (50 mL)
  6. washwashed with water (2×15 mL) and brine (15 mL)
  7. dry with materialThe organic layer was dried (MgSO4)
  8. concentrationconcentrated on a rotary evaporator
  9. customto give the crude product, which
  10. customwas purified by flash chromatography
  11. washto elute the product
  12. additionThe fractions containing the product
  13. concentrationconcentrated on a rotary evaporator

Quellen und Nachweise

ORD-Eintrag
ord-82ed5d1d32a244fc8f267fc4a2209125
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354432B2

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