Acetic Acid → N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-1-(trifluoroacetyl)piperidin-4-amine

HRID 1510645Notes

Reaction equation

HRID 1510645 reaction equation
Cl.[F:2][C:3]([F:14])([F:13])[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([NH2:12])[CH2:8][CH2:7]1)=[O:5].[O:15]1[C:20]2[CH:21]=[CH:22][C:23]([CH:25]=O)=[CH:24][C:19]=2[O:18][CH2:17][CH2:16]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[O:15]1[C:20]2[CH:21]=[CH:22][C:23]([CH2:25][NH:12][CH:9]3[CH2:10][CH2:11][N:6]([C:4](=[O:5])[C:3]([F:2])([F:13])[F:14])[CH2:7][CH2:8]3)=[CH:24][C:19]=2[O:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2481272,3-Dihydro-1,4-benzodioxin-6-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 866331901-(4-Aminopiperidin-1-YL)-2,2,2-trifluoroethan-1-one hydrochloride

Product 1

HCID 57815185N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-1-(trifluoroacetyl)piperidin-4-amineYield 94.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1.0 g of 1-(trifluoroacetyl)piperidin-4-amine hydrochloride in 20 mL of dichloromethane, 0.71 g of 2,3-dihydro-1,4-benzodioxine-6-carbaldehyde and 0.25 mL of acetic acid were added, and the mixture was stirred at room temperature for 2 hours. To the reaction mixture, 1.37 g of sodium triacetoxyborohydride was added, and the mixture was stirred at the same temperature for 30 minutes. The solvent was distilled off under reduced pressure, water and ethyl acetate were then added thereto, and the mixture was adjusted to pH 1.5 with 1 mol/L hydrochloric acid. The aqueous layer was separated and washed with ethyl acetate, thereto was added ethyl acetate, and the aqueous layer was adjusted to pH 7.8 with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 1.4 g of N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-1-(trifluoroacetyl)piperidin-4-amine as a colorless oily substance.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred at the same temperature for 30 minutes
  3. distillationThe solvent was distilled off under reduced pressure, water and ethyl acetate
  4. additionwere then added
  5. customThe aqueous layer was separated
  6. washwashed with ethyl acetate
  7. additionwas added ethyl acetate
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with ethyl acetate
  10. washthe resultant solution was washed with a saturated aqueous sodium chloride solution
  11. dry with materialdried over anhydrous magnesium sulfate
  12. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-72fcb10166644b799d76abd5c24038cb
Source dataset
uspto-grants-2012_07
Patent number
US08211908B2

Reaction notes

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