Triethylamine → 4-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1887068Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1887068
N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:32][C:33]1[C:42]([OH:43])=[CH:41][CH:40]=[C:39]2[C:34]=1[CH:35]=[CH:36][N:37]=[CH:38]2.[C:44]([N:51]1[CH2:56][CH2:55][CH:54](O)[CH2:53][CH2:52]1)([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45].C(N(CC)CC)C>ClCCl>[C:47]([O:46][C:44]([N:51]1[CH2:56][CH2:55][CH:54]([O:43][C:42]2[C:33]([Br:32])=[C:34]3[C:39](=[CH:40][CH:41]=2)[CH:38]=[N:37][CH:36]=[CH:35]3)[CH2:53][CH2:52]1)=[O:45])([CH3:50])([CH3:48])[CH3:49]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 1360928955-Bromo-6-isoquinolinol

Produkt 1

HCID 576469744-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl esterAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

3.75 mL (4.15 g, 23.8 mmol) of diethyl azo dicarboxylate were added to 12.7 g (19.9 mmol) of polymer-bound triphenylphosphine (PS—PPh3, approx. 1.6 mmol/g, Argonaut) in 250 mL of dichloromethane at 0° C. and stirred for 15 min. 4.45 g (19.9 mmol) 5-bromo isoquinoline-6-ol (9), 4.0 g (19.9 mmol) Boc-(4-hydroxy)piperidine and 4.1 mL (3.0 g, 29.8 mmol) triethyl amine were added. The mixture was shaken for 16 h. The polymer was removed by filtration through Celite and the solvents were distilled off. 20 mL dichloromethane were added and the precipitate was isolated by filtration. The crude product (8 g) was purified by flash chromatography using ethyl acetate/n-heptane as eluent to give 4.78 g (60%) of compound 11.

Aufarbeitung

  1. stirringThe mixture was shaken for 16 h
  2. customThe polymer was removed by filtration through Celite
  3. distillationthe solvents were distilled off
  4. addition20 mL dichloromethane were added
  5. customthe precipitate was isolated by filtration
  6. customThe crude product (8 g) was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-0ee76063be824d758c65e0de94648d44
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08501736B2

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