Potassium Carbonate → methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate

HRID 630301Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 630301
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[CH2:17][C@@H:16]3[CH2:18][C@H:13]2[CH2:14][N:15]3C(OC(C)(C)C)=O)=[CH:7][CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+]>Cl>[C@H:13]12[CH2:18][C@H:16]([NH:15][CH2:14]1)[CH2:17][N:12]2[CH2:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=1

Komponenten

4

Edukt 2

HCID 11430Potassium CarbonateHCID 71213169tert-Butyl (1S,4S)-5-(4-(methoxycarbonyl)benzyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Produkt 1

HCID 68488731methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoateAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 313Hydrochloric AcidLösungsmittel

Versuchsvorschrift

1,1-Dimethylethyl (1S,4S)-5-[[4-(methoxycarbonyl)phenyl]methyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (44.1 g, 127.3 mmol) was slurried in HCl (2 M in water, 0.6 L). The solid went into solution over 2 hours, and the solution was stirred for another 16 hours. The reaction was cooled to −5 C and saturated K2CO3 was added slowly enough to keep the temperature below 0 C to prevent ester hydrolysis. Once the pH was 11, the solution was extracted with CH2Cl2 until no product was observed in the water layer by TLC (3×). The combined organic fractions were concentrated under vacuum to obtain pure methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate (30.3 g, 97%) as the freebase; 1H NMR (CD3OD) δ 7.98 (d, 2H), 7.49 (d, 2H), 4.00 (sbr, 1H), 3.90 (s, 3H), 3.88 (d, 1H), 3.80 (d, 1H), 3.57 (sbr, 1H), 3.39 (ddbr, 1H), 3.03 (ddbr, 1H), 2.88 (ddbr, 1H), 2.72 (ddbr, 1H), 2.09 (dbr, 1H), 1.75 (dbr, 1H) ppm.

Aufarbeitung

  1. additionwas added slowly enough
  2. extractionOnce the pH was 11, the solution was extracted with CH2Cl2 until no product
  3. concentrationThe combined organic fractions were concentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-9abd60c1dbb8474583d348cdfa1dc46c
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315509B2

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