Piperidine, 1-(2-chloroethyl)-, hydrochloride → 7-Nitro-4-(2-(piperidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine

HRID 1917167Notes

Reaction equation

HRID 1917167 reaction equation
[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][N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl.[OH-].[Na+].O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:12]([CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:11][CH2:10][S:9][C:8]=2[CH:13]=1)([O-:3])=[O:2]

Participants

7

Reactant 2

HCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochlorideHCID 204961217-Nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine

Product 1

HCID 591441037-Nitro-4-(2-(piperidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazineYield 59.8%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 7-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine (1 g, 5.10 mmol), 1-(2-chloroethyl)piperidine 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 overnight (16 hours). The mixture was diluted with dichloromethane (5 mL) and water (20 mL), and the mixture was then transferred to a separatory funnel. The organic layer was removed, and the aqueous layer was extracted in 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; solvent gradient: dichloromethane 3CV, ramp to 6:94 (2M NH3 in methanol):CH2Cl2 over 15CV; 254 nm monitoring wavelength; flow=45 mL/minute), to give an orange solid (0.937 g, 59.8%). 1H-NMR (DMSO-d6) δ 7.85-7.81 (m, 2H), 6.82 (d, J=9.0 Hz, 1H), 3.82-3.79 (m, 2H), 3.58 (t, J=6.9 Hz, 2H), 3.08-3.04 (m, 2H), 2.50-2.45 (m, 2H), 2.44-2.34 (m, 4H), 1.49-1.46 (m, 4H), 1.40-1.37 (m, 2H); ESI-MS (m/z, %): 308 (MH+, 100).

Workup

  1. customthe mixture was then transferred to a separatory funnel
  2. customThe organic layer was removed
  3. extractionthe aqueous layer was extracted in 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; solvent gradient: dichloromethane 3CV, ramp to 6:94 (2M NH3 in methanol):CH2Cl2 over 15CV; 254 nm monitoring wavelength; flow=45 mL/minute)

Sources & evidence

ORD record
ord-80dccc5ea5054b0c99ac5fa85488e6de
Source dataset
uspto-grants-2013_12
Patent number
US08618286B2

Reaction notes

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