Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 86622676, compound

HRID 1946607Notes

Reaction equation

HRID 1946607 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([N:9]2[CH2:14][C@@H:13]3[CH2:15][C@H:10]2[CH2:11][N:12]3[C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[NH2:53][OH:54]>N1C=CC=CC=1>[C:1]([C:3]1[CH:4]=[C:5]([N:9]2[CH2:14][C@@H:13]3[CH2:15][C@H:10]2[CH2:11][N:12]3[C:16]2[CH:17]=[CH:18][C:19]([C:20]([NH:53][OH:54])=[O:21])=[CH:23][CH:24]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2]

Participants

5

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 443297Hydroxyamine hydrochlorideHCID 67007111HCID 67007111, compound

Product 1

HCID 86622676HCID 86622676, compoundYield 91.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Title compound 248 (0.21 g, 0.590 mmol) and BOP (0.287 g, 0.649 mmol) were combined and pyridine (5.90 ml) was added. The mixture was stirred 15 min. Hydroxylamine hydrochloride (0.045 g, 0.649 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was concentrated, water and 3N HCl were added (to reach pH=5). This aqueous mixture was extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was dissolved in THF (3 mL) and MeOH (3 mL), 4M KOH (0.3 ml) was added and the homogenous mixture was concentrated partially. The resulting aq. solution was diluted with water and 3N HCl (0.4 ml) was added. The precipitate was filtered, washed with water and ether and pumped on Hi-Vac overnight to afford title compound 249 (0.18 g, 91%) as a pink solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.81 (s, 1H), 8.70 (d, J=1.8 Hz, 1H), 7.56 (d, J=8.7 Hz, 2H), 7.27 (t, J=7.9 Hz, 1H), 7.01 (s, 1H), 6.95 (d, J=7.6 Hz, 1H), 6.88 (d, J=8.6 Hz, 1H), 6.58 (d, J=8.6 Hz, 2H), 4.73 (d, J=5.1 Hz, 2H), 3.57 (d, J=9.4 Hz, 2H), 3.03 (t, J=10.1 Hz, 2H), 2.06 (s, 2H). LRMS (ESI): (calc.) 334.1 (found) 333.4 (MH)−.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. additionwater and 3N HCl were added (to reach pH=5)
  4. extractionThis aqueous mixture was extracted twice with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in THF (3 mL)
  10. additionMeOH (3 mL), 4M KOH (0.3 ml) was added
  11. concentrationthe homogenous mixture was concentrated partially
  12. additionThe resulting aq. solution was diluted with water and 3N HCl (0.4 ml)
  13. additionwas added
  14. filtrationThe precipitate was filtered
  15. washwashed with water and ether
  16. custompumped on Hi-Vac overnight

Sources & evidence

ORD record
ord-de2e26949b854636b18d8ed9629c3624
Source dataset
uspto-grants-2013_03
Patent number
US08399452B2

Reaction notes

Loading…