Triethylamine → 3-(4-(4-(3-(4-Imidazolyl)acryloyl)piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yioxymethyl)oxazolidin-2-one

HRID 1167442Notes

Reaction equation

HRID 1167442 reaction equation
[NH:1]1[CH:5]=[C:4]([CH:6]=[CH:7][C:8]([OH:10])=O)[N:3]=[CH:2]1.S(Cl)(Cl)=O.Cl.Cl.[N:17]1([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:33][C@H:32]([CH2:34][O:35][C:36]4[CH:40]=[CH:39][O:38][N:37]=4)[O:31][C:30]3=[O:41])=[CH:25][C:24]=2[F:42])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(N(CC)CC)C>ClCCl.CN(C=O)C>[NH:1]1[CH:5]=[C:4]([CH:6]=[CH:7][C:8]([N:20]2[CH2:19][CH2:18][N:17]([C:23]3[CH:28]=[CH:27][C:26]([N:29]4[CH2:33][C@H:32]([CH2:34][O:35][C:36]5[CH:40]=[CH:39][O:38][N:37]=5)[O:31][C:30]4=[O:41])=[CH:25][C:24]=3[F:42])[CH2:22][CH2:21]2)=[O:10])[N:3]=[CH:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 69980303HCID 69980303, compoundHCID 178525355Npc125754

Product 1

HCID 1785205143-(4-(4-(3-(4-Imidazolyl)acryloyl)piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yioxymethyl)oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

3-(4-Imidazolyl)acrylic acid (690 mg, 5 mmol) was suspended in anhydrous dichloromethane (5 ml) under nitrogen, and thionyl chloride (10 ml) and one drop of DMF added. The mixture was stirred at ambient temperature for 18 hours, excess thionyl chloride was evaporated, and the residue azeotroped with dichloromethane (2×50 ml). The acid chloride was suspended in dichloromethane (30 ml), cooled to 4°, and a solution of 3-(4-(piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one dihydrochloride (866 mg, 2 mmol) and triethylamine (2.02 g, 20 mmol) in anhydrous dichloromethane (25 ml) added dropwise. The mixture was stirred for 18 hours at ambient temperature, and insoluble material filtered. The organic layer was treated with water (50 ml), further insoluble material removed, then washed with brine and dried over magnesium sulfate. After evaporation to dryness, the residue was dissolved in ethanol (5 ml) and treated with an excess of ethanol saturated with hydrogen chloride, to precipitate the desired product as a hydrochloride salt (122 mg).

Workup

  1. customexcess thionyl chloride was evaporated
  2. customthe residue azeotroped with dichloromethane (2×50 ml)
  3. temperaturecooled to 4°
  4. stirringThe mixture was stirred for 18 hours at ambient temperature
  5. filtrationinsoluble material filtered
  6. additionThe organic layer was treated with water (50 ml), further insoluble material
  7. customremoved
  8. washwashed with brine
  9. dry with materialdried over magnesium sulfate
  10. customAfter evaporation to dryness
  11. dissolutionthe residue was dissolved in ethanol (5 ml)
  12. additiontreated with an excess of ethanol saturated with hydrogen chloride
  13. customto precipitate the desired product as a hydrochloride salt (122 mg)

Sources & evidence

ORD record
ord-9e4ecd4c542a4a85ac9494ac7e78f145
Source dataset
uspto-grants-2003_09
Patent number
US06617339B1

Reaction notes

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