Cesium carbonate → HCID 86728125, compound

HRID 627656Notes

Reaction equation

HRID 627656 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[C:17]([CH3:40])([CH3:39])[S:18](=[O:38])(=[O:37])[C:19]([CH2:34][CH2:35][OH:36])([CH3:33])[C@:20]([C:23]2[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=2F)([CH3:22])[N:21]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[NH4+].[Cl-]>[CH3:40][C:17]1([CH3:39])[S:18](=[O:38])(=[O:37])[C:19]2([CH3:33])[CH2:34][CH2:35][O:36][C:24]3[CH:25]=[CH:26][C:27]([N+:29]([O-:31])=[O:30])=[CH:28][C:23]=3[C@@:20]2([CH3:22])[N:21]=[C:16]1[N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 2

HCID 10796Cesium carbonate2×HCID 86728124HCID 86728124, compound

Product 1

HCID 86728125HCID 86728125, compoundYield 43.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of crude tert-butyl N-tert-butoxycarbonyl-N-[(5R)-5-(2-fluoro-5-nitro-phenyl)-6-(2-hydroxyethyl)-2,2,5,6-tetramethyl-1,1-dioxo-1,4-thiazin-3-yl]carbamate (0.18 g, 0.31 mmol) in DMF (1.8 ml) was added cesium carbonate (0.25 g, 0.77 mmol). The resulting mixture was stirred at ambient temperature for 7 h. Extra cesium carbonate (0.36 g) was added and the mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with 30 ml of saturated NH4Cl and extracted with EtOAc. The organic extract was washed with brine and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude material as an orange oil. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Biotage column (25 g), eluting with a gradient of 5% to 40% EtOAc in hexane, to provide tert-butyl N-[(11bR)-3,3,4a,11b-tetramethyl-10-nitro-4,4-dioxo-5,6-dihydro-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (0.076 g, 43% yield) as a light-yellow solid. m/z (ESI) 591.1 (M+Na)+.

Workup

  1. stirringthe mixture was stirred at ambient temperature overnight
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as an orange oil
  9. customThe crude material was absorbed onto a plug of silica gel
  10. custompurified by chromatography through a Biotage column (25 g)
  11. washeluting with a gradient of 5% to 40% EtOAc in hexane

Sources & evidence

ORD record
ord-0a1cc6bd3c7e4c15b23cb0ef9f4ebe17
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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