Hydroxylamine → HCID 76637602, compound

HRID 1093104Notes

Reaction equation

HRID 1093104 reaction equation
[Cl:1][CH2:2][CH2:3][CH:4]1[O:8][CH2:7][C:6]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]#[N:10])[CH2:5]1.[NH2:22][OH:23].[C:24]([C:31]([O:33][CH2:34][CH3:35])=[O:32])#[C:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>C1COCC1>[NH2:10][C:9](=[N:22][O:23][C:25](=[CH:24][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:6]1([NH:11][C:12]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:21])[CH2:5][CH:4]([CH2:3][CH2:2][Cl:1])[O:8][CH2:7]1

Participants

5

Reactant 3

HCID 787HydroxylamineHCID 69803Diethyl acetylenedicarboxylateHCID 57905113HCID 57905113, compound

Product 1

HCID 76637602HCID 76637602, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of benzyl 5-(2-chloroethyl)-3-cyanotetrahydrofuran-3-ylcarbamate (0.86 g, 2.79 mmol) and 50% aq. hydroxylamine (0.853 mL, 13.93 mmol) in THF (25 mL) was stirred at room temperature for 18 h. The mixture was concentrated and the residue was redissolved in EtOH (20 mL) and treated with diethyl acetylenedicarboxylate (0.490 mL, 3.06 mmol) at room temperature. After 24 h, the reaction mixture was concentrated and the resulting pale yellow residue was taken up in Et2O (75 mL), washed with 1% aq. NH4OH (20 mL), water (20 mL) followed by brine (20 mL), then dried (Na2SO4), filtered, concentrated and purified by flash column chromatography on silica gel column using 1:3, 2:3 and 1:1 ethyl acetate/hexane to afford diethyl 2-(amino(3-(benzyloxycarbonylamino)-5-(2-chloroethyl)tetrahydrofuran-3-yl)methyleneaminooxy)but-2-enedioate (1.1707 g, 2.287 mmol, 82% yield) as a pale yellow paste. 1H NMR (500 MHz, CDCl3) δ: 7.30-7.39 (5 H, m), 5.75-5.88 (2 H, m), 5.26-5.62 (2 H, m), 5.05-5.12 (2 H, m), 4.21-4.37 (3 H, m), 4.12-4.20 (3 H, m), 4.02-4.10 (1 H, m), 3.57-3.67 (2 H, m), 2.60-2.85 (1 H, m), 1.87-2.20 (3 H, m), 1.29-1.38 (3 H, m), 1.22-1.28 (3 H, m). LCMS (M+H) calcd for C23H31ClN3O8: 512.18; found: 512.25.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was redissolved in EtOH (20 mL)
  3. concentrationthe reaction mixture was concentrated
  4. washwashed with 1% aq. NH4OH (20 mL), water (20 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash column chromatography on silica gel column

Sources & evidence

ORD record
ord-87a7356b12b541e08352e6a1255ca570
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

Loading…