Methyl iodide → (2S,4S)-4-methoxypyrrolidine-2-carboxylic acid

HRID 1360376Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1360376
C(OC([N:11]1[CH2:15][C@@H:14]([OH:16])[CH2:13][C@H:12]1[C:17]([OH:19])=[O:18])=O)C1C=CC=CC=1.[H-].[Na+].[CH3:22]I.[H][H]>C1COCC1.CO.[OH-].[OH-].[Pd+2]>[CH3:22][O:16][C@@H:14]1[CH2:15][NH:11][C@H:12]([C:17]([OH:19])=[O:18])[CH2:13]1

Komponenten

8

Edukt 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 688414(2S,4S)-1-((Benzyloxy)carbonyl)-4-hydroxypyrrolidine-2-carboxylic acidHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 12849452(2S,4S)-4-methoxypyrrolidine-2-carboxylic acidAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9942167Palladium hydroxideKatalysatorHCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A stirred solution of (2S,4S)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (35.9 g, 135.4 mmol) in dry THF (870 mL) is treated under nitrogen with sodium hydride (11.78 g, 491 mmol) and methyl iodide (38.5 g, 271 mmol), using a procedure similar to that published in J. Med. Chem. 1988, 31, 875, except that reflux is carried out for 16 h. The crude extracted product of this alkylation reaction, (2S,4S)-1-(benzyloxycarbonyl)-4-methoxypyrrolidine-2-carboxylic acid, is then dissolved in methanol (200 mL), treated with 6.2 g of 20% palladium hydroxide on carbon, and stirred at room temperature overnight under 1 atmosphere of hydrogen. The reaction mixture is filtered, washed with methanol, and evaporated in vacuo. The resulting solid is suspended in dichloromethane (450 mL) and filtered to give 11.5 g (91%) of the pure title compound: MS: 146 (M+H)+; 500 MHz 1H NMR (d6-DMSO) δ

Aufarbeitung

  1. extractionThe crude extracted
  2. customproduct of this alkylation reaction, (2S,4S)-1-(benzyloxycarbonyl)-4-methoxypyrrolidine-2-carboxylic acid
  3. filtrationThe reaction mixture is filtered
  4. washwashed with methanol
  5. customevaporated in vacuo
  6. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-382f2acd97754fa8a6d475c4dad39c86
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07879855B2

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