Sodium hydride → HCID 178449911, compound

HRID 1931129Notes

Reaction equation

HRID 1931129 reaction equation
[C:1]([NH:5][OH:6])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.C(NO)(C)(C)C.C(=O)(O)[O-].[Na+].[H-].[Na+].[C:24]([C:28]1[S:32]/[C:31](=[N:33]\[C:34](=[O:46])[C:35]2[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=2F)/[N:30]([CH2:47][CH2:48][CH2:49][C:50]#[N:51])[N:29]=1)([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[C:1]([NH:5][O:6][C:36]1[CH:37]=[CH:38][C:39]([C:41]([F:42])([F:43])[F:44])=[CH:40][C:35]=1[C:34](/[N:33]=[C:31]1\[S:32][C:28]([C:24]([CH3:25])([CH3:27])[CH3:26])=[N:29][N:30]\1[CH2:47][CH2:48][CH2:49][C:50]#[N:51])=[O:46])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 98586N-tert-butylhydroxylamineHCID 516892Sodium BicarbonateHCID 9877417tert-Butylhydroxylamine acetateHCID 178441918HCID 178441918, compound

Product 1

HCID 178449911HCID 178449911, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-tert-butylhydroxylamine (133 mg, 1.50 mmol) (prepared from commercially available N-tert-butylhydroxylamine acetate (Aldrich) by adding saturated sodium bicarbonate solution and extracting the free base with ethyl ether) in anhydrous THF (10 mL) was added sodium hydride (53.9 mg, 1.35 mmol). The mixture was stirred at 0° C. for 20 min. A solution of Example 151A (310 mg, 0.75 mmol) in THF (4 mL) was added and the mixture was stirred at 22° C. for 5 hours. The solvent was removed under reduced pressure and the residue was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried with MgSO4 and concentrated under reduced pressure. The residue was purified by chromatography on SiO2 using an Analogix® Intelliflash280™ (Hexanes-EtOAc: 0-50% gradient) to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.22 (s, 9H), 1.42 (s, 9H), 2.23-2.37 (m, 2H), 2.48 (t, J=7.1 Hz, 2H), 4.54 (t, J=6.5 Hz, 2H), 5.75 (s, 1H), 7.61 (dd, J=8.7, 2.4 Hz, 1H), 7.83 (d, J=8.7 Hz, 1H), 8.28 (d, J=2.4 Hz, 1H); MS (ESI) m/z 484 (M+H)+.

Workup

  1. extractionextracting the free base with ethyl ether) in anhydrous THF (10 mL)
  2. stirringthe mixture was stirred at 22° C. for 5 hours
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was partitioned between water and ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on SiO2 using an Analogix® Intelliflash280™ (Hexanes-EtOAc: 0-50% gradient)

Sources & evidence

ORD record
ord-c3dbfd8a917a49fd9f2475c0d8e3fe3b
Source dataset
uspto-grants-2012_05
Patent number
US08188135B2

Reaction notes

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