Acetic Acid → 1-(4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester

HRID 2374385Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2374385
C([BH3-])#N.[Na+].[CH2:5]([O:8][C:9]([C:11]1[N:12]([NH2:16])[CH:13]=[CH:14][CH:15]=1)=[O:10])[CH:6]=[CH2:7].[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH:22]=O)=[CH:20][CH:19]=1.C(O)(=O)C>CO>[CH2:5]([O:8][C:9]([C:11]1[N:12]([NH:16][CH2:22][C:21]2[CH:24]=[CH:25][C:18]([F:17])=[CH:19][CH:20]=2)[CH:13]=[CH:14][CH:15]=1)=[O:10])[CH:6]=[CH2:7]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 680234-FluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 598535721-amino-1H-pyrrole-2-carboxylic acid allyl ester

Produkt 1

HCID 598535761-(4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl esterAusbeute 37,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

Sodium cyanoborohydride (2.29 g, 36.4 mmol) was added to a solution of 1-amino-1H-pyrrole-2-carboxylic acid allyl ester (Example 1b, 3.03 g, 18.2 mmol), 4-fluorobenzaldehyde (1.96 mL, 18.3 mmol) and acetic acid (6 mL), in methanol (120 mL) at 25° C. The reaction mixture was stirred at 25° C. for 18 h, and then was concentrated in vacuo to a volume of about 30 mL. The remaining liquid was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and a 1:1 mixture of ethyl acetate and hexanes (2×200 mL). The organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (Merck silica gel 60, 40-63 μm, 0→40% ethyl acetate in hexanes) afforded the desired product, 1-(4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester (1.87 g, 6.8 mmol, 37% yield) as a clear liquid. 1H NMR (400 MHz, CDCl3) δ: 4.08 (2H, d, J=5.4 Hz), 4.75-4.77 (1H, m), 5.27-5.30 (1H, m), 5.37-5.41 (1H, m), 5.95-5.97 (1H, m), 5.98-6.05 (1H, m), 6.58-6.61 (1H, m), 6.75-6.76 (1H, m), 6.89-6.91 (1H, m), 6.97-7.01 (2H, m), 7.22-7.25 (2H, m).

Aufarbeitung

  1. concentrationwas concentrated in vacuo to a volume of about 30 mL
  2. customThe remaining liquid was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL)
  3. additiona 1:1 mixture of ethyl acetate and hexanes (2×200 mL)
  4. dry with materialThe organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash column chromatography (Merck silica gel 60, 40-63 μm, 0→40% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-5d76dc3885174b4b97c10b48b905c805
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07462611B2

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