Hydroxylamine → (3s, 4r)-4-[4-(2-Methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid hydroxyamide

HRID 736738Notes

Reaction equation

HRID 736738 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([S:20]([NH:23][CH:24]3[CH2:29][CH2:28][O:27][CH2:26][CH:25]3[C:30](O)=[O:31])(=[O:22])=[O:21])=[CH:16][CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[OH:33][N:34]1C2C=CC=CC=2N=N1.Cl.C(N=C=N)C.NO>CN(C=O)C>[OH:33][NH:34][C:30]([C@H:25]1[C@H:24]([NH:23][S:20]([C:17]2[CH:18]=[CH:19][C:14]([O:13][CH2:12][C:10]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=[C:2]([CH3:1])[CH:11]=3)=[CH:15][CH:16]=2)(=[O:22])=[O:21])[CH2:29][CH2:28][O:27][CH2:26]1)=[O:31]

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 757711-HydroxybenzotriazoleHCID 21883477Ethylcarbodiimide hydrochlorideHCID 688206984-[4-(2-Methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid

Product 1

HCID 87586561(3s, 4r)-4-[4-(2-Methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid hydroxyamideYield 6.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid (0.280 g, 0.658 mmol) and 1-hydroxybenzotriazole (HOBT, 0.177 g, 1.32 mmol) in DMF (10 mL) was added 1-(3-dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (0.253 g, 1.32 mmol) at 0° C. The reaction mixture stirred at 0° C. for 10 min, then warmed to 25° C. over 1 h. After recooling the reaction to 0° C. hydroxylamine (50% by wt in water, 0.6 mL, 6.6 mmol) was added. The reaction was allowed to warm to 25° C. over 19 h. The DMF was removed in vacuo and the resulting oil was diluted with ethyl acetate (100 mL) and this mixture was then washed with saturated aqueous sodium bicarbonate (3×30 mL) and brine (30 mL). The organic layer was dried over MgSO4, filtered and concentrated to obtain a crude solid (0.170 g) which was purified by Biotage Flash 40S chromatography, eluting with 4% methanol in ethyl acetate, to afford (3S,4R)-4-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid hydroxyamide as an amorphous white solid (0.02 g, 6.6%) that was a 75.7:24.3 mixture of enantiomers, as determined by analytical chiral HPLC (Chiralpak IA column, 7:3 n-propanol/heptane, 1 mL/min, 254 nm). MS: 472 (M+H)+

Workup

  1. temperaturewarmed to 25° C. over 1 h
  2. additionwas added
  3. temperatureto warm to 25° C. over 19 h
  4. customThe DMF was removed in vacuo
  5. additionthe resulting oil was diluted with ethyl acetate (100 mL)
  6. washthis mixture was then washed with saturated aqueous sodium bicarbonate (3×30 mL) and brine (30 mL)
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto obtain a crude solid (0.170 g) which
  11. customwas purified by Biotage Flash 40S chromatography
  12. washeluting with 4% methanol in ethyl acetate

Sources & evidence

ORD record
ord-3be14ce9ce464504ae0221dcace51852
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

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