1-Hydroxybenzotriazole → 4-(2-{4-[(4-Fluorophenyl)amino]-1-piperidinyl}-2-oxoethyl)benzaldehyde

HRID 43338Notes

Reaction equation

HRID 43338 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1)=[O:2].[F:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:16][CH:15]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C=O)C>[F:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][CH:21]2[CH2:26][CH2:25][N:24]([C:10](=[O:12])[CH2:9][C:6]3[CH:5]=[CH:4][C:3]([CH:1]=[O:2])=[CH:8][CH:7]=3)[CH2:23][CH2:22]2)=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 4778193N-(4-Fluorophenyl)-4-piperidinamineHCID 113441872-(4-formylphenyl)acetic Acid

Product 1

HCID 252238954-(2-{4-[(4-Fluorophenyl)amino]-1-piperidinyl}-2-oxoethyl)benzaldehydeYield 82.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of D3 (87 mg, 0.53 mmol), D2 (102 mg, 0.53 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (123 mg, 0.64 mmol), and 1-hydroxybenzotriazole (98 mg, 0.64 mmol) in DMF (2 ml) was stirred at room temperature overnight. The DMF was removed in vacuo then EtOAc and water were added. The product was extracted into EtOAc and the combined organic layers were washed with saturated aq. NaHCO3 solution (×2) and brine then dried (Na2SO4). The solvent was removed in vacuo and the resulting residue was purified by chromatography eluting with an EtOAc/petroleum ether gradient to afford the title compound (149 mg). MS (ES): MH+ 341.

Workup

  1. customThe DMF was removed in vacuo
  2. additionEtOAc and water were added
  3. extractionThe product was extracted into EtOAc
  4. washthe combined organic layers were washed with saturated aq. NaHCO3 solution (×2) and brine
  5. dry with materialthen dried (Na2SO4)
  6. customThe solvent was removed in vacuo
  7. customthe resulting residue was purified by chromatography
  8. washeluting with an EtOAc/petroleum ether gradient

Sources & evidence

ORD record
ord-ec9adf3f78b34a0eb346907f339131fd
Source dataset
uspto-grants-2013_09
Patent number
US08536182B2

Reaction notes

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