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

HRID 969442Notes

Reaction equation

HRID 969442 reaction equation
C([O-])([O-])=O.[K+].[K+].[CH2:7]([CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[CH2:8][CH2:9][CH3:10].Cl[CH2:18][CH2:19][CH2:20][N:21]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[S:24][CH2:23][C:22]1=[O:31].CO>C(#N)C>[CH2:7]([CH:11]1[CH2:16][CH2:15][N:14]([CH2:18][CH2:19][CH2:20][N:21]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[S:24][CH2:23][C:22]2=[O:31])[CH2:13][CH2:12]1)[CH2:8][CH2:9][CH3:10]

Participants

6

Reactant 4

HCID 887MethanolHCID 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 1

HCID 6342AcetonitrileSolvent2×

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 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. waitfor 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-9ff9f7554e4845ef83ecf1d3bc1a430c
Source dataset
uspto-grants-2007_12
Patent number
US07307075B2

Reaction notes

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