Ethyl Acrylate → tert-butyl (3RS,4RS)-4-[4-(2-ethoxycarbonyl-vinyl)-phenyl]-3-hydroxy-piperidine-1-carboxylate

HRID 1004992

Reaktionsgleichung

Reaktionsgleichung von HRID 1004992
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]2[OH:21])=[CH:4][CH:3]=1.[C:22]([O:26][CH2:27][CH3:28])(=[O:25])[CH:23]=[CH2:24].C([O-])(=O)C.[Na+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[CH2:27]([O:26][C:22]([CH:23]=[CH:24][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]2[OH:21])=[CH:4][CH:3]=1)=[O:25])[CH3:28]

Komponenten

7

Edukt 3

HCID 8821Ethyl AcrylateHCID 517045Sodium AcetateHCID 54537313tert-butyl (3RS,4RS)-4-(4-bromophenyl)-3-hydroxy-piperidine-1-carboxylate

Produkt 1

HCID 86604399tert-butyl (3RS,4RS)-4-[4-(2-ethoxycarbonyl-vinyl)-phenyl]-3-hydroxy-piperidine-1-carboxylateAusbeute 77,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 80271Tri-o-tolylphosphineKatalysator2×HCID 167845palladium(II) acetateKatalysator2×HCID 6228DimethylformamideLösungsmittel3×

Versuchsvorschrift

A Schlenk tube was charged under argon with 25.6 mg (0.114 mmol) of Pd(OAc)2, 69.6 mg (0.Z29 mmol) of tri(o-tolyl)phosphine and 20 ml of DMF (distilled under argon) and the reaction mixture was stirred at room temperature for 1 5 minutes. A 200 ml sulphonation flask was charged under argon and while stirring with 8.15 g (22.9 mmol) of tert-butyl (3RS,4RS)-4-(4-bromo-phenyl)-3-hydroxy-piperidine-1-carboxylate [Example 25 (c)], 100 ml of DMF, 3.73 ml (34.3 mmol) of ethyl acrylate, 2.25 g (27.5 mmol) of sodium acetate and the yellow catalyst solution. The reaction mixture was stirred at 120° C. for 6 hours. In order to complete the reaction, a solution of 5.1 mg Pd(OAc)2 and 14.3 mg of tri(o-tolyl)phosphine in 5 ml of DMF was added after 5 hours. The dark reaction mixture was evaporated on a rotary evaporator. The grey solid residue was taken up in ether and the turbid solution was washed three times with water, dried over sodium sulphate and evaporated under reduced pressure. The yellow solid residue was chromatographed on 250 g of silica gel using a 2:1 mixture of hexane and ethyl acetate as the eluent. After crystallization from ethyl acetate there were obtained 6.66 g (77% of theory) of tert-butyl (3RS,4RS)-4-[4-(2-ethoxycarbonyl-vinyl)-phenyl]-3-hydroxy-piperidine-1-carboxylate as colourless crystals; MS: 376 (M+H)+.

Aufarbeitung

  1. additionA 200 ml sulphonation flask was charged under argon
  2. stirringThe reaction mixture was stirred at 120° C. for 6 hours
  3. customthe reaction
  4. customThe dark reaction mixture
  5. customwas evaporated on a rotary evaporator
  6. washthe turbid solution was washed three times with water
  7. dry with materialdried over sodium sulphate
  8. customevaporated under reduced pressure
  9. customThe yellow solid residue was chromatographed on 250 g of silica gel using
  10. additiona 2:1 mixture of hexane and ethyl acetate as the eluent
  11. customAfter crystallization from ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-e84ca2e1e50445ec9ae75d455ce7f9eb
Quelldatensatz
uspto-grants-2000_04
Patentnummer
US06051712

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