Sodium hydride → tert-butyl ((11bR)-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate

HRID 627603Notes

Reaction equation

HRID 627603 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[C@:11]1([CH3:32])[C@H:16]([CH2:17][CH2:18][OH:19])[S:15](=[O:21])(=[O:20])[C:14]([CH3:23])([CH3:22])[C:13]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[N:12]1.[H-].[Na+]>C1COCC1.CN(C=O)C>[CH3:23][C:14]1([CH3:22])[S:15](=[O:20])(=[O:21])[CH:16]2[CH2:17][CH2:18][O:19][C:2]3[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=3[C@@:11]2([CH3:32])[N:12]=[C:13]1[NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30]

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 90307364tert-butyl ((5R,6S)-5-(2-fluoro-5-nitrophenyl)-6-(2-hydroxyethyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate

Product 1

HCID 90307368tert-butyl ((11bR)-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamateYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of crude tert-butyl ((5R,6S)-5-(2-fluoro-5-nitrophenyl)-6-(2-hydroxyethyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (250 mg, 0.528 mmol) in THF (5 ml) and DMF (0.5 ml) was treated portionwise with NaH (60% suspension in mineral oil) (52.8 mg, 1.320 mmol). After initial gas evolution the reaction mixture became dark red. The mixture was stirred at RT for 10 min. The mixture was quenched with NH4Cl solution and diluted with EtOAc. Water was added to dissolve solids, and the organic layer was separated, washed with brine and concentrated. The residue was purified by FC on 12 g RedSep Gold column using 10-100% EtOAc in heptane. All the fractions containing both epimers were combined and concentrated to afford tert-butyl ((11bR)-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (196 mg, 0.432 mmol, 82% yield) as a mixture of epimers at C4. Ratio by NMR 2:1 favoring trans-isomer.

Workup

  1. customThe mixture was quenched with NH4Cl solution
  2. additiondiluted with EtOAc
  3. additionWater was added
  4. dissolutionto dissolve solids
  5. customthe organic layer was separated
  6. washwashed with brine
  7. concentrationconcentrated
  8. customThe residue was purified by FC on 12 g RedSep Gold column
  9. additionAll the fractions containing both epimers
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-d248e6a0f0564970a2c9b0d0f13b36ed
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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