Formaldehyde → 6-Dimethylamino-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17614Notes

Reaction equation

HRID 17614 reaction equation
F[C:2](F)(F)C(O)=O.[C:8]([C:10]1[C:15]2[N:16]=[C:17]([CH:19]3[CH2:21][CH2:20]3)[O:18][C:14]=2[C:13]([F:22])=[C:12]([NH:23][C:24](=O)OC(C)(C)C)[C:11]=1[CH3:31])#[N:9].C=O.C([BH3-])#N.[Na+]>C(OCC)(=O)C>[CH3:2][N:23]([CH3:24])[C:12]1[C:13]([F:22])=[C:14]2[O:18][C:17]([CH:19]3[CH2:20][CH2:21]3)=[N:16][C:15]2=[C:10]([C:8]#[N:9])[C:11]=1[CH3:31]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 86630883tert-Butyl (4-cyano-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazol-6-yl)carbamate

Product 1

HCID 685839996-Dimethylamino-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrileYield 42%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Trifluoroacetic acid (5 ml) was added to tert-butyl (4-cyano-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazol-6-yl)carbamate (I-318) (70 mg, 0.211 mmol), followed by stirring at room temperature for 1 hour. The reaction liquid was evaporated under reduced pressure, and the resulting residue was dissolved in acetic acid (2 ml). 38% formaldehyde (153 μl, 2.11 mmol) was added to the solution, then sodium cyanoborohydride (70 mg, 2.11 mmol) was added, followed by stirring at room temperature for 1 hour. Ethyl acetate was added to the reaction liquid, followed by washing with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated away under reduced pressure. The resulting residue was purified by preparative TLC (eluent, ethyl acetate:n-hexane=3:1, v/v) to obtain the entitled compound (23 mg, 42%) as a white crystal.

Workup

  1. customThe reaction liquid
  2. customwas evaporated under reduced pressure
  3. dissolutionthe resulting residue was dissolved in acetic acid (2 ml)
  4. stirringby stirring at room temperature for 1 hour
  5. washby washing with saturated brine
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated away under reduced pressure
  8. customThe resulting residue was purified by preparative TLC (eluent, ethyl acetate

Sources & evidence

ORD record
ord-9baa8aedcc3b4cc4916b9ad71e959bd0
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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