4-Methylmorpholine → (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide

HRID 2223551Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2223551
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:16][C@@H:17]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:18]([OH:20])=O)[C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:41][CH2:42][C:43]#[N:44].P(O)([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C(OCC)(=O)C>[C:42]([CH2:43][NH:44][C:18](=[O:20])[C@@H:17]([NH:16][C@@H:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[CH2:21][CH:22]([CH3:23])[CH3:24])#[N:41]

Komponenten

8

Edukt 5

HCID 79724-Methylmorpholine2×HCID 24203Sodium Phosphate, DibasicHCID 62365Isobutyl chloroformateHCID 11491918Aminoacetonitrile hydrochlorideHCID 67298368HCID 67298368, Verbindung

Produkt 1

HCID 86590549(2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid (1.17 g, 2.86 mmol) in THF (20 mL) at −10° C. were added 4-methylmorpholine (0.315 mL, 2.86 mmol) and isobutyl chloroformate (0.371 mL, 2.86 mmol). The reaction mixture was stirred for 10 minutes, whereupon aminoacetonitrile hydrochloride (0.318 g, 3.43 mmol) was added, followed by 4-methylmorpholine (0.315 mL, 2.86 mmol). The solution was stirred for 90 minutes. Ethyl acetate (30 mL) and aqueous disodium phosphate (30 mL) were added. The organic phase was separated, washed with brine, dried over MgSO4, and evaporated to dryness. The product was purified on a short plug of silica gel (10-50% ethyl acetate/hexane gradient elution) to give (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid cyanomethylamide.

Aufarbeitung

  1. additionwas added
  2. customThe organic phase was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe product was purified on a short plug of silica gel (10-50% ethyl acetate/hexane gradient elution)

Quellen und Nachweise

ORD-Eintrag
ord-4058e85466bd4fd888b99defeb2627f0
Quelldatensatz
uspto-grants-2008_05
Patentnummer
US07375134B2

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