Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1) → 4-(2-(1-Methylpyrrolidin-2-yl)ethyl)-7-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine

HRID 424506Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 424506
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[NH:12][CH2:11][CH2:10][S:9][C:8]=2[CH:13]=1)([O-:3])=[O:2].Cl.Cl[CH2:16][CH2:17][CH:18]1[CH2:22][CH2:21][CH2:20][N:19]1[CH3:23]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl.[OH-].[Na+].O>[CH3:23][N:19]1[CH2:20][CH2:21][CH2:22][CH:18]1[CH2:17][CH2:16][N:12]1[CH2:11][CH2:10][S:9][C:8]2[CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][C:7]1=2

Komponenten

7

Edukt 2

HCID 3017050Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1)HCID 204961217-Nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine

Produkt 1

HCID 591440834-(2-(1-Methylpyrrolidin-2-yl)ethyl)-7-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazineAusbeute 52,8 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 74236Tetrabutylammonium BromideKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 14798Sodium HydroxideLösungsmittel

Versuchsvorschrift

A mixture of 7-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine (1 g, 5.10 mmol), 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride (1.876 g, 10.19 mmol), and tetrabutylammonium bromide (0.082 g, 0.255 mmol) in dichloromethane (10 mL) and 50% NaOH solution (10 mL) was stirred at room temperature for 16 hours (overnight). The reaction was then diluted with dichloromethane (5 mL) and water (20 mL), and the mixture was transferred to a separatory funnel. The organic layer was removed, and the aqueous layer was extracted into dichloromethane (2×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The red crude material was subjected to column chromatography on silica gel using the Biotage purification system (80 g silicycle column; gradient: dichloromethane 3CV then ramp to 6:94 (2M NH3 in methanol):dichloromethane over 15CV; 254 nm; flow: 45 mL/min) to give the title compound as yellow-orange solid (0.827 g, 52.8%). 1H-NMR (DMSO-d6) δ 7.87 (dd, J=3.0, 9.0 Hz, 1H), 7.83 (d, J=3.0 Hz, 1H), 6.79 (d, J=9.3 Hz, 1H), 3.79-3.76 (m, 2H), 3.46 (t, J=8.1 Hz, 2H), 3.08-3.05 (m, 2H), 2.99-2.92 (m, 1H), 2.23 (s, 3H), 2.10-2.06 (m, 2H), 1.92-1.78 (m, 2H), 1.66-1.61 (m, 2H), 1.54-1.47 (m, 2H); ESI-MS (m/z, %): 308 (MH+, 100).

Aufarbeitung

  1. customthe mixture was transferred to a separatory funnel
  2. customThe organic layer was removed
  3. extractionthe aqueous layer was extracted into dichloromethane (2×10 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe Biotage purification system (80 g silicycle column

Quellen und Nachweise

ORD-Eintrag
ord-04966b1728184519bae6295573f25a9c
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08106043B2

Notizen zur Reaktion

Wird geladen…