4-Methylmorpholine → (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 604810Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 604810
[C:1]([N:8]1[CH2:16][C@H:14]([OH:15])[CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[CH2:32]([O:34][C:35]([C@@:37]1([NH2:42])[CH2:39][C@H:38]1[CH:40]=[CH2:41])=[O:36])[CH3:33]>C1COCC1>[C:4]([O:3][C:1]([N:8]1[CH2:16][C@H:14]([OH:15])[CH2:13][C@H:9]1[C:10](=[O:12])[NH:42][C@:37]1([C:35]([O:34][CH2:32][CH3:33])=[O:36])[CH2:39][C@H:38]1[CH:40]=[CH2:41])=[O:2])([CH3:5])([CH3:6])[CH3:7]

Komponenten

6

Edukt 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 10820795rac-ethyl (1R,2S)-1-amino-2-ethenylcyclopropane-1-carboxylate

Produkt 1

HCID 57892908(2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-23 °C

Versuchsvorschrift

To a solution of 4.87 g (21.0 mmol) of Boc-(2S,4R)-hydroxyproline in 25 mL of THF was added 2.03 mL (20.0 mmol) of N-methylmorpholine. A suspension formed. The mixture was cooled to −23° C. and 2.85 g (20.0 mmol) of isobutylchloroformate was added. After stirring for 10 min additional 4.25 g (42.0 mmol) of N-methylmorpholine was added. To this mixture was added the solution of (1R,2S)-1-amino-2-vinyl-cyclopropanecarboxylic acid ethyl ester prepared in example 1 at a temperature of −15° C. within 5 min. The reaction mixture was stirred for 2.5 h at 0° C. The salts were filtered off and the filtrate was treated with 20 mL of aqueous HCl (0.5 N). The solvents were removed at 50° C. under reduced pressure using a rotary evaporator and the residue was extracted twice with 50 mL of ethyl acetate. The extract was washed with 40 mL of water and 40 mL of aqueous sodium carbonate solution (10% w/w), and dried over sodium sulfate. Finally the solvent was removed completely to give 8.19 g of (2S,4R)-2-((1R,2S)-1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester as a yellow oil. The product was used in the next step without further purification.

Aufarbeitung

  1. customA suspension formed
  2. additionwas added
  3. filtrationThe salts were filtered off
  4. additionthe filtrate was treated with 20 mL of aqueous HCl (0.5 N)
  5. customThe solvents were removed at 50° C. under reduced pressure
  6. customa rotary evaporator
  7. extractionthe residue was extracted twice with 50 mL of ethyl acetate
  8. washThe extract was washed with 40 mL of water and 40 mL of aqueous sodium carbonate solution (10% w/w)
  9. dry with materialdried over sodium sulfate
  10. customFinally the solvent was removed completely

Quellen und Nachweise

ORD-Eintrag
ord-934fb5e7eb1b4223a14cfae8562eeac6
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07910728B2

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