1-(2-Chloroethyl)pyrrolidine hydrochloride → 7-nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine

HRID 424500Notes

Reaction equation

HRID 424500 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[CH2:22][CH2:21][CH2:20][CH2:19]1>[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].C(Cl)Cl.[OH-].[Na+].O>[NH3:1].[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:12]([CH2:16][CH2:17][N:18]3[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

8

Reactant 2

HCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 204961217-Nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine

Product 2

HCID 222AmmoniaHCID 591441207-nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazineYield 84.2%

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)pyrrolidine hydrochloride (1.734 g, 10.19 mmol), and nBu4NBr (0.082 g, 0.255 mmol) in CH2Cl2 (10 mL) and 50% NaOH solution (10 mL) was stirred at room temperature for 16 hours. The mixture was diluted with CH2Cl2 (25 mL) and water (50 mL). The mixture was transferred to a separatory funnel, and the layers were separated. The aqueous layer was extracted in CH2Cl2 (2×25 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The red crude material was subjected to flash chromatography on silica gel (CH2Cl2, then 1.75-5% (2M NH3 in MeOH)/CH2Cl2) to give 7-nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine as a brown viscous oil (0.63 g, 42%). 1H NMR (DMSO-d6) δ 7.86-7.82 (m, 2H), 6.82 (d, J=9.0 Hz, 1H), 3.81 (t, J=4.8 Hz, 2H), 3.58 (t, J=6.9 Hz, 2H), 3.33 (s, 4H), 3.05 (t, J=5.1 Hz, 2H), 2.63 (t, J=6.9 Hz, 2H), 2.50 (s, 4H), 1.67 (s, 4H); ESI-MS (m/z, %): 296, 294 (MH+, 100), 98 (13).

Workup

  1. customThe mixture was transferred to a separatory funnel
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted in CH2Cl2 (2×25 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-d7369050f9c4488b8df358b309242b31
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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