Sodium Azide → HCID 86732135, compound

HRID 930306Notes

Reaction equation

HRID 930306 reaction equation
O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[N-]=[N+]=[N-].[Na+].Br[C:19]1[N:24]=[C:23]([C@:25]2([CH3:43])[CH2:30][C@@H:29]([C:31]([F:34])([F:33])[F:32])[O:28][C:27]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[N:26]2)[C:22]([F:44])=[CH:21][CH:20]=1.C[NH:46][C@@H]1CCCC[C@H]1NC>[Cu]I.O>[NH2:46][C:19]1[N:24]=[C:23]([C@:25]2([CH3:43])[CH2:30][C@@H:29]([C:31]([F:34])([F:33])[F:32])[O:28][C:27]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[N:26]2)[C:22]([F:44])=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 33557Sodium AzideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 23667548Sodium AscorbateHCID 86732136HCID 86732136, compound

Product 1

HCID 86732135HCID 86732135, compoundYield 230.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A sealable vial was charged with (+)-sodium L-ascorbate (0.026 g, 0.13 mmol, Aldrich), sodium azide (0.102 g, 1.56 mmol, Aldrich), copper(I) iodide (0.026 g, 0.13 mmol, Acros), and tert-butyl ((4S,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate (7i, 0.238 g, 0.52 mmol). The sealed vial was evacuated and backfilled with Nitrogen. EtOH (2.5 mL) was added followed by water (1 mL) and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.021 mL, 0.130 mmol, Aldrich). The reaction mixture was heated to 70° C. for 3 hs. The cooled reaction mixture was partitioned between NH4Cl/NH4OH (9:1) (10 mL) and EtOAc (10 mL). The organic layer was separated, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified via silica gel flash chromatography (gradient 10-50% EtOAc in hexanes) to afford the title compound as a white solid (0.119 g, 0.3 mmol, 58% yield). MS m/z=393.2 [M+H]+. Calculated for C16H20F4N4O3: 392.3

Workup

  1. customThe sealed vial was evacuated
  2. additionEtOH (2.5 mL) was added
  3. customThe cooled reaction mixture
  4. customwas partitioned between NH4Cl/NH4OH (9:1) (10 mL) and EtOAc (10 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified via silica gel flash chromatography (gradient 10-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-81f4d065c9014b48ab8519c02962e8cc
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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