Sodium Azide → HCID 54675652, compound

HRID 2203374Notes

Reaction equation

HRID 2203374 reaction equation
Br[CH2:2][CH:3]1[CH2:5][CH2:4]1.[N-:6]=[N+:7]=[N-:8].[Na+].[N-]=[N+]=[N-].[NH2:13][C:14]1[C:15]2[C:37]([C:39]#[CH:40])([CH3:38])[C:36](=[O:41])[NH:35][C:16]=2[N:17]=[C:18]([C:20]2[C:28]3[C:23](=[N:24][CH:25]=[CH:26][CH:27]=3)[N:22]([CH2:29][CH2:30][C:31]([F:34])([F:33])[F:32])[N:21]=2)[N:19]=1.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CN(C=O)C.[Al].S([O-])([O-])(=O)=O.[Cu+2].O>[NH2:13][C:14]1[C:15]2[C:37]([C:39]3[N:6]=[N:7][N:8]([CH2:2][CH:3]4[CH2:5][CH2:4]4)[CH:40]=3)([CH3:38])[C:36](=[O:41])[NH:35][C:16]=2[N:17]=[C:18]([C:20]2[C:28]3[C:23](=[N:24][CH:25]=[CH:26][CH:27]=3)[N:22]([CH2:29][CH2:30][C:31]([F:33])([F:32])[F:34])[N:21]=2)[N:19]=1

Participants

10

Reactant 5

HCID 33557Sodium AzideHCID 33558AzideHCID 81503BromomethylcyclopropaneHCID 23667548Sodium AscorbateHCID 86679011HCID 86679011, compound

Product 1

HCID 54675652HCID 54675652, compound

Reagents, catalysts & solvents 4

HCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 5359268AluminumSolvent

Procedure

To (bromomethyl)cyclopropane (150 mg, 0.822 mmol) in DMF (2492 μl) was added sodium azide (50.2 mg, 0.772 mmol) in a 4 mL vial wrapped in aluminum foil. The solution was left to stir for 16 hours at rt. To the azide solution was added water (1.5 mL), the intermediate from Step C (100 mg, 0.249 mmol), copper(II) sulfate (15.91 mg, 0.100 mmol) and sodium ascorbate (49.4 mg, 0.249 mmol). The solution was heated to 40° C. and stirred for an additional 24 h. The reaction was then filtered through a pad of Celite™ (diatomaceous earth) and partitioned between EtOAc and water. The organic layer was separated, dried (sodium sulfate) and concentrated in vacuo under vacuum. Purification by silica gel column chromatography using a hexanes/EtOAc gradient afforded the product as a white solid. Chiral separation using SFC provided both enantiomers of the title compound. 1H NMR (500 MHz, CHCl2-d): δ 8.86 (dd, J=8.06, 1.59 Hz, 1H); 8.58 (dd, J=4.52, 1.57 Hz, 1H); 7.71 (s, 1H); 7.22 (dd, J=8.08, 4.50 Hz, 1H); 4.90 (dd, J=9.19, 6.28 Hz, 2H); 4.25-4.13 (m, 2H); 2.95-2.83 (m, 2H); 1.88 (s, 3H); 1.33-1.24 (m, 1H); 0.73-0.68 (m, 2H); 0.45-0.41 (m, 2H). m/z=499.1 (M+H).

Workup

  1. waitThe solution was left
  2. temperatureThe solution was heated to 40° C.
  3. stirringstirred for an additional 24 h
  4. filtrationThe reaction was then filtered through a pad of Celite™ (diatomaceous earth)
  5. custompartitioned between EtOAc and water
  6. customThe organic layer was separated
  7. dry with materialdried (sodium sulfate)
  8. concentrationconcentrated in vacuo under vacuum
  9. customPurification by silica gel column chromatography

Sources & evidence

ORD record
ord-d36569d8f56a4fde8c6afc0a98cf04bd
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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