Sodium Iodide → 4-[3-(4-Butyl-piperidin-1-yl)propyl]-4H-benzo[1,4]thiazin-3-one

HRID 2102650Notes

Reaction equation

HRID 2102650 reaction equation
[Na+].[I-].C([O-])([O-])=O.[K+].[K+].[CH2:9]([CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)[CH2:10][CH2:11][CH3:12].Cl[CH2:20][CH2:21][CH2:22][N:23]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[S:26][CH2:25][C:24]1=[O:33]>C(#N)C.CO>[CH2:9]([CH:13]1[CH2:18][CH2:17][N:16]([CH2:20][CH2:21][CH2:22][N:23]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[S:26][CH2:25][C:24]2=[O:33])[CH2:15][CH2:14]1)[CH2:10][CH2:11][CH3:12]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 132838674-ButylpiperidineHCID 689124944-(3-Chloropropyl)-4H-benzo[1,4]thiazin-3-one

Product 1

HCID 99501364-[3-(4-Butyl-piperidin-1-yl)propyl]-4H-benzo[1,4]thiazin-3-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

NaI (1.24 g, 8.27 mmol), K2CO3 (1.14 g, 8.27 mmol), and 4-butylpiperidine (0.62 g, 4.34 mmol) in acetonitrile (10 mL) were stirred at rt. 4-(3-chloropropyl)-4H-benzo[1,4]thiazin-3-one (1.0 g, 4.14 mmol) in acetonitrile (15 mL) was added via a syringe. The reaction was stirred at 60° C. for 13 hours and then at 80° C. for another 25 hours under nitrogen atmosphere and concentrated in vacuo. Water (150 mL) was added and the reaction mixture was extracted with ethyl acetate (3×150 mL). The combined organic phases were dried (Na2SO4) and concentrated in vacuo to give 1.63 g of crude. The crude product was subjected to CC[eluent:EtOAC:MeOH(100:1-5%)] to give the pure title compound. Yield 1.06 g 74.2% HPLC-MS [M+H]+ 347 (UV/MS(%)=100/99. 1H NMR (CDCl3): δ 0.88 (t, 3H), 1.23 (m, 9H), 1.64 (d, 2H), 1.85 (m, 4H), 2.34 (t, 2H), 2.83 (d, 2H), 3.36 (s, 1H), 4.03 (t, 2H), 6.99 (m, 1H), 7.22 (d, 2H), 7.34 (d, 1H), 13C NMR (CDCl3): δ 14.21, 23.03, 25.23, 29.15, 31.80, 32.63, 35.90, 36.44, 43.28, 54.26, 55.91, 118.18, 123.45, 124.17, 127.27, 128.56, 139.63, 165.19.

Workup

  1. waitat 80° C. for another 25 hours under nitrogen atmosphere
  2. concentrationconcentrated in vacuo
  3. additionWater (150 mL) was added
  4. extractionthe reaction mixture was extracted with ethyl acetate (3×150 mL)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto give 1.63 g of crude

Sources & evidence

ORD record
ord-a24db91132c048ad8570705d9ca86e97
Source dataset
uspto-grants-2009_08
Patent number
US07576078B2

Reaction notes

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