Sodium hydride → HCID 178449912, compound

HRID 536766Notes

Reaction equation

HRID 536766 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][C@H:48]2[CH2:52][CH2:51][CH2:50][O:49]2)[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:44])[F:43])=[CH:40][C:35]=1[C:34](/[N:33]=[C:31]1\[S:32][C:28]([C:24]([CH3:27])([CH3:25])[CH3:26])=[N:29][N:30]\1[CH2:47][C@H:48]1[CH2:52][CH2:51][CH2:50][O:49]1)=[O:46])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 98586N-tert-butylhydroxylamineHCID 516892Sodium BicarbonateHCID 9877417tert-Butylhydroxylamine acetateHCID 178441932HCID 178441932, compound

Product 1

HCID 178449912HCID 178449912, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-tert-butylhydroxylamine (145 mg, 1.62 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 (58.4 mg, 1.46 mmol). The mixture was stirred at 0° C. for 20 minutes. A solution of Example 153A (350 mg, 0.81 mmol) in THF (4 mL) was added and the mixture was stirred at 0° C. for 3 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, filtered, 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), 1.74-1.89 (m, 1H), 1.88-2.08 (m, 3H), 3.74-3.84 (m, 1H), 3.89-4.00 (m, 1H), 4.29 (dd, J=12.0, 4.7 Hz, 1H), 4.45-4.63 (m, 2H), 5.73 (s, 1H), 7.59 (dd, J=8.8, 3.1 Hz, 1H), 7.80 (d, J=8.8 Hz, 1H), 8.33 (d, J=2.4 Hz, 1H); MS (ESI) m/z 501 (M+H)+.

Workup

  1. extractionextracting the free base with ethyl ether) in anhydrous THF (10 mL)
  2. stirringthe mixture was stirred at 0° C. for 3 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. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by chromatography on SiO2 using an Analogix® Intelliflash280™ (Hexanes-EtOAc: 0-50% gradient)

Sources & evidence

ORD record
ord-2f2eb6dc97004e0b8b519a9586395df7
Source dataset
uspto-grants-2014_10
Patent number
US08859596B2

Reaction notes

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