Acetohydroxamic Acid → HCID 178475149, compound

HRID 82777Notes

Reaction equation

HRID 82777 reaction equation
[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:23])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=2F)/[N:7]([CH2:24][C@H:25]2[CH2:29][CH2:28][CH2:27][O:26]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:30][NH:31][C:32](=[O:34])[CH3:33].CC(C)([O-])C.[Na+]>C1COCC1.CCOCC>[C:32]([NH:31][O:30][C:13]1[CH:14]=[CH:15][C:16]([C:18]([F:20])([F:21])[F:19])=[CH:17][C:12]=1[C:11](/[N:10]=[C:8]1\[S:9][C:5]([C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:6][N:7]\1[CH2:24][C@H:25]1[CH2:29][CH2:28][CH2:27][O:26]1)=[O:23])(=[O:34])[CH3:33]

Participants

6

Reactant 3

HCID 1990Acetohydroxamic AcidHCID 23676156Sodium t-butoxideHCID 178441320HCID 178441320, compound

Product 1

HCID 178475149HCID 178475149, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of Example 1A (150 mg, 0.35 mmol) and N-hydroxyacetamide (52.3 mg, 0.70 mmol) in THF (10 mL) was added sodium tert-butoxide (67.0 mg, 0.70 mmol). The mixture was stirred at room temperature for 6 hours. The reaction mixture was diluted with ether and washed with brine. The aqueous phase was extracted with ether (2×20 mL), dried over MgSO4, and filtered. The mixture was concentrated under reduced pressure and the residue was purified by FC on SiO2 using an Analogix® Intelliflash280™ (eluted with Hexanes-EtOAc: 0-30%) to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.19 (s, 9 H), 1.21 (m, 1 H), 1.37 (s, 1 H), 1.94 (s, 2 H), 1.97-2.11 (m, 1 H), 3.65-3.92 (m, 2 H), 3.99-4.33 (m, 2 H), 4.34-4.55 (m, 1 H), 6.82 (s, 1 H), 7.66 (dd, J=9.2, 2.4 Hz, 1 H), 8.34 (d, J=8.8 Hz, 1 H), 8.61 (d, J=2.4 Hz, 1 H); MS (ESI) m/z 486 (M+H)+.

Workup

  1. washwashed with brine
  2. extractionThe aqueous phase was extracted with ether (2×20 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationThe mixture was concentrated under reduced pressure
  6. customthe residue was purified by FC on SiO2 using
  7. washan Analogix® Intelliflash280™ (eluted with Hexanes-EtOAc: 0-30%)

Sources & evidence

ORD record
ord-605045b6e5f846708f13c3081bf527c6
Source dataset
uspto-grants-2014_09
Patent number
US08846730B2

Reaction notes

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