Triethylamine → HCID 11814324, compound

HRID 1596050Notes

Reaction equation

HRID 1596050 reaction equation
[F:1][C:2]([F:45])([F:44])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([S:16]([N:19]([CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[C:32]=3[C:41]([OH:43])=O)[C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[CH:6][CH:5]=1.C(Cl)(=O)C(Cl)=O.Cl.[NH2:53][OH:54].C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C.C1COCC1.O.C(OCC)(=O)C>[OH:54][NH:53][C:41]([C:32]1[C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:39]=[CH:40][C:31]=1[CH2:30][N:19]([S:16]([C:13]1[CH:14]=[CH:15][C:10]([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:44])[F:45])=[CH:5][CH:6]=2)=[CH:11][CH:12]=1)(=[O:17])=[O:18])[C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])=[O:43]

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 443297Hydroxyamine hydrochlorideHCID 11767389HCID 11767389, compound

Product 1

HCID 11814324HCID 11814324, compoundYield 410%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an ice cold solution of Example 9G (1.096 g, 1.72 mmol) in CH2Cl2 (12 mL) under N2 was added DMF (5 drops) and oxalyl chloride (0.30 mL, 3.45 mmol), and the reaction was allowed to stir at room temperature for 1 hour. The solvent was then removed by rotary evaporation chasing with anhydrous toluene (5 mL), and the residue was taken up in CH2Cl2 (7 mL) and added to a 0° C. solution of hydroxylamine hydrochloride (1.21 g, 0.017 mol) and triethylamine (2.9 mL, 0.021 mol) in THF/H20 (2:1 v/v, 12 mL). After allowing the reaction mixture to stir at room temperature for 3 hours, ethyl acetate (100 mL) and H2O (25 mL) were added, the layers were separated, and the organic phase was washed with 1 M HCl (2×10 mL), saturated aqueous NaHCO3 (10 mL), brine, dried (Na2SO4), filtered, and concentrated. The residue was triturated with CH2Cl2 (75 mL) and vacuum filtered to remove a solid impurity. The filtrate was concentrated and the residue purified on silica gel (1.9×6 cm) with a gradient of CH2Cl2 to 3% MeOH/CH2Cl2 +0.5% concentrated NH4OH to obtain 0.459 g (410%) of the desired compound as light beige solid.

Workup

  1. customThe solvent was then removed by rotary evaporation
  2. stirringto stir at room temperature for 3 hours
  3. customthe layers were separated
  4. washthe organic phase was washed with 1 M HCl (2×10 mL), saturated aqueous NaHCO3 (10 mL), brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was triturated with CH2Cl2 (75 mL) and vacuum
  9. filtrationfiltered
  10. customto remove a solid impurity
  11. concentrationThe filtrate was concentrated
  12. customthe residue purified on silica gel (1.9×6 cm) with a gradient of CH2Cl2 to 3% MeOH/CH2Cl2 +0.5% concentrated NH4OH

Sources & evidence

ORD record
ord-ca0db3b60e284e9982855e99e5953ea6
Source dataset
uspto-grants-2001_09
Patent number
US06288261B1

Reaction notes

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