Water → HCID 70278038, compound

HRID 481337Notes

Reaction equation

HRID 481337 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[CH:6]=[C:5]2[O:18][CH2:19]CO.CS(Cl)(=O)=O.[CH3:27]S([O-])(=O)=[O:29].[CH3:32][NH:33][CH2:34][CH2:35][N:36]1[CH2:40][CH2:39][NH:38][C:37]1=[O:41].[OH2:42]>ClCCl.C(C(C)=O)C(C)C.C(N(CC)CC)C>[C:37]([OH:41])(=[O:29])/[CH:3]=[CH:4]\[C:5]([OH:18])=[O:42].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[CH:6]=[C:5]2[O:18][CH2:19][CH2:32][N:33]([CH3:27])[CH2:34][CH2:35][N:36]1[CH2:40][CH2:39][NH:38][C:37]1=[O:41]

Participants

9

Reactant 5

HCID 962WaterHCID 31297Methanesulfonyl chlorideHCID 85257Methanesulfonate2×HCID 10486963HCID 10486963, compoundHCID 10852136HCID 10852136, compound2×

Product 1

HCID 70278038HCID 70278038, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 7909Methyl Isobutyl KetoneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 2-[5-chloro-1-(4-fluorophenyl)-3-1H-indolyloxy]ethanol (2a) (4.8, 0.016 mol) and triethylamine (5 mL) in dichloromethane (50 mL), a solution of methanesulfonyl chloride (1.9 mL, 0.025 mol) in dichloromethane (16 mL) was added at 0°-5° C. over 0.5 h. After stirring for 3 h at room temperature the reaction mixture was washed with water (2×100 mL), dried (Na2SO4) and the solvents were evaporated in vacuo. Excess of methanesulfonyl chloride was removed by concentrating the remaining oil with toluene in vacuo several times. The crude methanesulfonate of 2a (6.0 g, 0.016 mol) was used without further purification. A mixture of the crude methanesulfonate, 2-(methylamino)ethyl-2-imidazolidinone (4.9 g, 0.034 mol), K2 CO3 (4.0 g, 0.029 mol) and methyl isobutyl ketone was refluxed for 18 h. After cooling to room temperature water (100 mL) was added and the resulting mixture was extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (100 mL) and brine (100 mL), and dried (Na2SO4). Evaporation of the solvents and purification by column chromatography on silica gel (eluted with ethyl acetate/ethanol 5:1 containing 4% triethylamine) afforded the title compound (4.2 g, 61%) as an oil. The title compound crystallized as its maleate from ethyl acetate: mp 183°-185° C.; 1H NMR (DMSO-d6) δ 2.85 (s, 3 H), 3.20-3.55 (m, 8 H), 3.65 (broad s, 2 H), 4.40 (broad t, 2 H) 6.05 (s, 2 H), 6.65 (broad s, 1 H), 7.2, (broad d, 1 H), 7.45 (t, 2 H), 7.55 (d, 1 H), 7.69 (7.55, 1 H), 7.60 (dd, 2 H), 7.70 (broad s, 1 H). MS (m/z) 431 (MH+, 2), 170 (33), 113 (100); Anal. (C22H24ClFN4O2.C4H4O4) C, H, N.

Workup

  1. washwas washed with water (2×100 mL)
  2. dry with materialdried (Na2SO4)
  3. customthe solvents were evaporated in vacuo
  4. customExcess of methanesulfonyl chloride was removed
  5. concentrationby concentrating the remaining oil with toluene in vacuo several times
  6. temperaturewas refluxed for 18 h
  7. additionwas added
  8. extractionthe resulting mixture was extracted with ethyl acetate (2×100 mL)
  9. washThe combined organic phases were washed with water (100 mL) and brine (100 mL)
  10. dry with materialdried (Na2SO4)
  11. customEvaporation of the solvents and purification by column chromatography on silica gel (eluted with ethyl acetate/ethanol 5:1 containing 4% triethylamine)

Sources & evidence

ORD record
ord-a328d999d25f4eda88540e434a52ad88
Source dataset
uspto-grants-1998_08
Patent number
US05789404

Reaction notes

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