Diisopropylethylamine → 3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzoic acid

HRID 20947

Reaktionsgleichung

Reaktionsgleichung von HRID 20947
C(O[C:6]([N:8]1[CH2:12][C@H:11]([OH:13])C[C@@H]1C(O)=O)=O)(C)(C)C.Br[C:18]1[CH:19]=[C:20]([CH:25]=[C:26]([C:28]([N:30]2[CH2:34][CH2:33][CH2:32][C@@H:31]2[CH2:35][O:36][CH3:37])=[O:29])[CH:27]=1)[C:21]([O:23]C)=[O:22].BrC1C=C(C=C(C(OC)=O)C=1)C(O)=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.COC[C@H]1CCCN1>ClCCl>[CH3:37][O:36][CH2:35][C@H:31]1[CH2:32][CH2:33][CH2:34][N:30]1[C:28]([C:26]1[CH:25]=[C:20]([CH:19]=[C:18]([C:6]2[O:13][CH:11]=[CH:12][N:8]=2)[CH:27]=1)[C:21]([OH:23])=[O:22])=[O:29]

Komponenten

8

Edukt 6

HCID 81531DiisopropylethylamineHCID 671216(2R)-2-(Methoxymethyl)pyrrolidineHCID 688616N-Boc-cis-4-hydroxy-D-prolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 225936413-Bromo-5-(methoxycarbonyl)benzoic acidHCID 67315972(R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate

Produkt 1

HCID 593468493-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzoic acidAusbeute 73 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Step H (1): (R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate. To a solution of 3-bromo-5-(methoxycarbonyl)benzoic acid (1.8 g, 6.95 mmol) in dichloromethane (100 mL) and was added Hunig's base (2.7 g, 20.85 mmol) to make a clear solution and HATU (3.17 g, 8.34 mmol) was then added. After stirring for 30 min, the reaction mixture was added (R)-2-(methoxymethyl)pyrrolidine (800 mg, 6.95 mmol) and the reaction mixture was stirred at rt for 6 h. Dichloromethane (100 mL) was added and the mixture was washed with 1N NaOH, H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient) to give 1.8 g of the title compound (73% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 1.77-2.08 (4H, m), 3.14-3.47 (5H, m), 3.63 (2H, brd s), 3.82 (3H, s), 4.41 (1H, brd s), 7.83 (1H, s), 8.07 (1H, s), 8.20 (1H, m).

Aufarbeitung

  1. additionwas then added
  2. stirringthe reaction mixture was stirred at rt for 6 h
  3. washthe mixture was washed with 1N NaOH, H2O
  4. concentrationconcentrated under vacuum
  5. customThe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient)

Quellen und Nachweise

ORD-Eintrag
ord-0cc5c90e166c4f5b9e2b634346869be7
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745470B2

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