Hydroxylamine → HCID 16661101, compound

HRID 1360650Notes

Reaction equation

HRID 1360650 reaction equation
[C:1]([C:5]1[CH:14]=[C:13]2[C:8]([CH2:9][CH2:10][N:11]([S:15]([CH2:18][CH:19]([CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)O)(=[O:17])=[O:16])[CH2:12]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.CS(Cl)(=O)=O.[NH2:39][OH:40].C(O[C:45](=[O:47])C)(=O)C>C1COCC1.C(O)=O>[C:1]([C:5]1[CH:14]=[C:13]2[C:8]([CH2:9][CH2:10][N:11]([S:15]([CH2:18][CH:19]([N:39]([OH:40])[CH:45]=[O:47])[CH:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)(=[O:17])=[O:16])[CH2:12]2)=[CH:7][CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 787HydroxylamineHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 57855496HCID 57855496, compound

Product 1

HCID 16661101HCID 16661101, compound

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-[(7-tert-butyl-3,4-dihydroisoquinolin-2(1H)-yl)sulfonyl]-1-(tetrahydro-2H-pyran-4-yl)ethanol (431 mg, 1.13 mmol) and Et3N (0.38 ml, 2.71 mmol) in anhydrous THF (10 ml) was cooled at 0° C., then methanesulfonyl chloride (0.105 ml, 1.36 mmol) was added dropwise. The resulting mixture was stirred at 0° C. for 15 min, then at 60° C. for 20 h00. A 50% aqueous solution of NH2OH (1.0 ml, 16.9 mmol)) was added and the resulting mixture was stirred at 60° C. for 2 h30. Then the reaction mixture was washed with brine (5 ml), dried (MgSO4) and the solvent was removed under reduced pressure to give a yellow oil. A mixture of formic acid (3.2 ml) and acetic anhydride (0.8 ml) was stirred at 0° C. for 30 min., then a solution of the previous oil in anhydrous THF (5 ml) was added and the resulting mixture was stirred at 0° C. for 10 min., then at RT for 30 min. The mixture was evaporated under reduced pressure. The residue was taken up with MeOH (10 ml) and heated at 60° C. for 30 min. The reaction mixture was evaporated under reduced pressure, then the residue was taken up with EtOAc (20 ml) and washed with water (2×10 ml), a saturated aqueous solution of NaHCO3 (10 ml) and brine (10 ml). The aqueous layers were extracted with EtOAc (20 ml). The organic layers were combined, dried (MgSO4) and the solvent was removed under reduced pressure to give a yellow oil. After purification by crystallization in EtOAc/Et2O/pentane, the title compound (66) was obtained as a white powder (175 mg, 36%). HPLC, Rt: 4.0 min (purity: 100%). LC/MS, M+(ESI): 425.3, M−(ESI): 422.9.

Workup

  1. customat 60° C.
  2. stirringthe resulting mixture was stirred at 60° C. for 2 h30
  3. washThen the reaction mixture was washed with brine (5 ml)
  4. dry with materialdried (MgSO4)
  5. customthe solvent was removed under reduced pressure
  6. customto give a yellow oil
  7. stirringwas stirred at 0° C. for 30 min.
  8. stirringthe resulting mixture was stirred at 0° C. for 10 min.
  9. waitat RT for 30 min
  10. customThe mixture was evaporated under reduced pressure
  11. temperatureheated at 60° C. for 30 min
  12. customThe reaction mixture was evaporated under reduced pressure
  13. washwashed with water (2×10 ml)
  14. extractionThe aqueous layers were extracted with EtOAc (20 ml)
  15. dry with materialdried (MgSO4)
  16. customthe solvent was removed under reduced pressure
  17. customto give a yellow oil
  18. customAfter purification
  19. customby crystallization in EtOAc/Et2O/pentane

Sources & evidence

ORD record
ord-df5f8938246d4dd282aad3fed578aa21
Source dataset
uspto-grants-2011_02
Patent number
US07879876B2

Reaction notes

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