Triethylamine → HCID 67979956, Verbindung

HRID 1622304Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1622304
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH3:17])([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH2:41]1[C:50]2[C:45](=[CH:46][C:47]([C:51]([O:53][CH3:54])=[O:52])=[CH:48][CH:49]=2)[CH2:44][CH2:43][NH:42]1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([C:14]([N:42]2[CH2:43][CH2:44][C:45]3[C:50](=[CH:49][CH:48]=[C:47]([C:51]([O:53][CH3:54])=[O:52])[CH:46]=3)[CH2:41]2)=[O:16])([CH3:17])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

6

Edukt 4

HCID 8471Triethylamine2×HCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 232828481-[(Tert-butoxy)carbonyl]-4-methylpiperidine-4-carboxylic acidHCID 42614607Methyl 1,2,3,4-tetrahydroisoquinoline-6-carboxylate hydrochloride

Produkt 1

HCID 67979956HCID 67979956, VerbindungAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 1-(tert-butoxycarbonyl)-4-methylpiperidine-4-carboxylic acid (0.830 g, 3.41 mmol) and triethylamine (0.792 mL, 5.68 mmol) in DMF (11.0 mL) was treated with TFFH (1.13 g, 4.26 mmol). The resulting mixture was stirred at rt for 30 min and then methyl 1,2,3,4-tetrahydroisoquinoline-6-carboxylate hydrochloride (0.647 g, 2.84 mmol) and triethylamine (0.792 mL, 5.68 mmol) were added. The reaction mixture was stirred at rt for 2 days and then extracted with EtOAc three times. The combined organic phases were washed with water and brine, dried over Na2SO4, filtered and concentrated. Purification of the resulting residue by column chromatography (SiO2, 0-100% EtOAc in hexane) provided methyl 2-{[1-(tert-butoxycarbonyl)-4-methylpiperidin-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (0.959 g, 82%). LC-MS: (FA) ES+ 439 (M+Na); 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J=10.1, 2.2 Hz, 2H), 7.19 (d, J=8.0 Hz, 1H), 4.79 (s, 2H), 3.95-3.77 (m, 5H), 3.67 (d, J=38.1 Hz, 2H), 3.21 (s, 2H), 2.92 (t, J=5.7 Hz, 2H), 2.24-2.10 (m, 2H), 1.61 (d, J=10.8 Hz, 1H), 1.44 (d, J=5.0 Hz, 10H), 1.33 (d, J=3.6 Hz, 3H).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at rt for 2 days
  2. extractionextracted with EtOAc three times
  3. washThe combined organic phases were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the resulting residue by column chromatography (SiO2, 0-100% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-efe5648b45ae4e7e82d391a52217d12f
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778931B2

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