Sodium hydride → HCID 86728112, compound

HRID 627643Notes

Reaction equation

HRID 627643 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([CH3:23])([CH3:22])[S:20](=[O:25])(=[O:24])[CH:19]([CH2:26]CCO)[C@@:18]([CH2:40][F:41])([C:30]2[CH:35]=[C:34]([N+:36]([O-:38])=[O:37])[CH:33]=[CH:32][C:31]=2F)[N:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].C1C[O:47][CH2:46]C1.CN(C=O)C>>[F:41][CH2:40][C@@:18]12[C:30]3[CH:35]=[C:34]([N+:36]([O-:38])=[O:37])[CH:33]=[CH:32][C:31]=3[O:47][CH2:46][CH2:26][C@@H:19]1[S:20](=[O:24])(=[O:25])[C:21]([CH3:23])([CH3:22])[C:16]([N:8]([C:9]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:15])[C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[N:17]2

Participants

4

Reactant 3

HCID 24758Sodium hydride2×HCID 21974620tetrahydrofuran N,N-dimethylformamideHCID 86728111HCID 86728111, compound

Product 1

HCID 86728112HCID 86728112, compoundYield 34%

Procedure

To a solution of tert-butyl N-tert-butoxycarbonyl-N-[(3S)-3-(fluoromethyl)-3-(2-fluoro-5-nitro-phenyl)-2-(3-hydroxypropyl)-6,6-dimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]carbamate (1.95 g, 3.30 mmol) in THF:DMF (10:1, 44 mL) at 0° C. was added NaH (264 mg, 6.60 mmol, 60% suspension in mineral oil) portion wise. The reaction mixture was stirred at RT for 1 h and an additional amount of NaH was added (264 mg, 6.60 mmol, 60% suspension in mineral oil). The reaction mixture was stirred at RT for 1 h, quenched with satd. aqueous NH4Cl, and diluted with EtOAc. Water was added to dissolve solids, and the organic layer was separated. The organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude mixture was purified by silica gel chromatography using a 0-25% EtOAc/hexanes gradient to afford the less polar cis-isomer, tert-butyl N-[(4aS,11bS)-11b-(fluoromethyl)-3,3-dimethyl-10-nitro-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (647 mg, 34%) as a white solid, LC/MS (ESI+) m/z=594 (M+Na), and the more polar trans-isomer, tert-butyl N-[(4aS,11bS)-11b-(fluoromethyl)-3,3-dimethyl-10-nitro-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (594 mg, 31%) as a white solid. LC/MS (ESI+) m/z=594 (M+Na).

Workup

  1. stirringThe reaction mixture was stirred at RT for 1 h
  2. customquenched with satd
  3. additionaqueous NH4Cl, and diluted with EtOAc
  4. additionWater was added
  5. dissolutionto dissolve solids
  6. customthe organic layer was separated
  7. washThe organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude mixture was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e8acd2dac95c42faa78b70f90271176e
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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