Carbon tetrabromide → Methyl 3-azidomethyl-5-fluoromethylbenzoate

HRID 473237Notes

Reaction equation

HRID 473237 reaction equation
[F:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH2:13]O)[CH:12]=1)[C:6]([O:8][CH3:9])=[O:7].[N-:15]=[N+:16]=[N-:17].[Na+].C(Br)(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C(N(CC)CC)C>[N:15]([CH2:13][C:11]1[CH:10]=[C:5]([CH:4]=[C:3]([CH2:2][F:1])[CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])=[N+:16]=[N-:17]

Participants

7

Reactant 4

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 67253567Methyl 3-fluoromethyl-5-hydroxymethylbenzoate

Product 1

HCID 86671517Methyl 3-azidomethyl-5-fluoromethylbenzoateYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Methyl 3-fluoromethyl-5-hydroxymethylbenzoate (34) (2.30 g, 11.6 mmol) was dried for 24 hours. Sodium azide (3.77 g, 58.1 mmol), carbon tetrabromide (4.24 g, 12.1 mmol), and triphenylphosphine (3.66 g, 13.9 mmol) were dried for 48 hours. Under Ar atmosphere, these were mixed with triethylamine (3.6 mL), dissolved in DMF (88 mL), and stirred for 93 hours at a room temperature. TLC was used to confirm the progress of the reaction. Then, the mixture was extracted with EtOAc. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the solvent. The residue was purified by neutral silica gel column chromatography (hexane:EtOAc=10:1) to isolate methyl 3-azidomethyl-5-fluoromethylbenzoate (35) (1.37 g, 53%) as a pale yellow oil.

Workup

  1. customthe progress of the reaction
  2. extractionThen, the mixture was extracted with EtOAc
  3. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. customevaporated under reduced pressure
  6. customto remove the solvent
  7. customThe residue was purified by neutral silica gel column chromatography (hexane:EtOAc=10:1)

Sources & evidence

ORD record
ord-7cb982ea968b4d24bcc82fc392c3b391
Source dataset
uspto-grants-2014_01
Patent number
US08633304B2

Reaction notes

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