Triethylamine → HCID 54109602, compound

HRID 2271030Notes

Reaction equation

HRID 2271030 reaction equation
[C:1](Cl)(=[O:5])[O:2][CH2:3][CH3:4].[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:18][C:17]([S:19]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][C@@H:23]3[C:28]([NH:30][O:31][CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)=[O:29])(=[O:21])=[O:20])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH2:3]([O:2][C:1]([N:25]1[CH2:26][CH2:27][N:22]([S:19]([C:17]2[S:18][C:14]([C:11]3[CH:12]=[CH:13][C:8]([F:7])=[CH:9][CH:10]=3)=[CH:15][CH:16]=2)(=[O:21])=[O:20])[C@@H:23]([C:28]([NH:30][O:31][CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)=[O:29])[CH2:24]1)=[O:5])[CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 53817994HCID 53817994, compound

Product 1

HCID 54109602HCID 54109602, compoundYield 82.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A solution of ethyl chlorocarbonate (42 mg) in CHCl3 (1 ml) was added dropwise to a solution of (2R)-1-[5-(4-fluorophenyl)thiophene-2-sulfonyl]-N-(2-tetrahydropyranyloxy)-2-piperazinecarboxamide (150 mg) and triethylamine (39 mg) in CHCl3 (2 ml) with cooling on an ice bath. The reaction mixture was stirred at said temperature for 30 minutes and the reaction was quenched by adding 3-(N,N-dimethylamino)propylamine (0.5 ml). The mixture was concentrated in vacuo, and the residue was partitioned between AcOEt and 5% aqueous citric acid. The organic layer was washed with saturated aqueous NaHCO3 solution and saturated aqueous NaCl solution, dried over MgSO4, and concentrated in vacuo. The residue was purified by SiO2 column chromatography eluted with AcOEt in hexane gradually from 40% to 60%, to give 142 mg of (2R)-4-ethoxycarbonyl-1-[5-(4-fluorophenyl)thiophene-2-sulfonyl]-N-(2-tetrahydropyranyloxy)-2-piperazinecarboxamide.

Workup

  1. temperaturewith cooling on an ice bath
  2. customfor 30 minutes
  3. customthe reaction was quenched
  4. additionby adding 3-(N,N-dimethylamino)propylamine (0.5 ml)
  5. concentrationThe mixture was concentrated in vacuo
  6. customthe residue was partitioned between AcOEt and 5% aqueous citric acid
  7. washThe organic layer was washed with saturated aqueous NaHCO3 solution and saturated aqueous NaCl solution
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by SiO2 column chromatography
  11. washeluted with AcOEt in hexane gradually from 40% to 60%

Sources & evidence

ORD record
ord-bd7dc85205ad40b6b5659f5f28a3de00
Source dataset
uspto-grants-2001_12
Patent number
US06333324B1

Reaction notes

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