1-Hydroxybenzotriazole → (S)-4-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-1-(3-hydroxy-propyl)-3-methyl-piperazin-2-one

HRID 559351Notes

Reaction equation

HRID 559351 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[F:13])[CH:5]=[CH:6][C:7]([OH:9])=[O:8].[OH:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][NH:21][C@@H:20]([CH3:24])[C:19]1=[O:25].C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.[ClH:45].C(N=C=NCCCN(C)C)C>CN(C)C=O>[CH2:2]([Cl:1])[Cl:45].[CH3:7][OH:8].[NH4+:18].[OH-:14].[Cl:1][C:2]1[CH:3]=[C:4](/[CH:5]=[CH:6]/[C:7]([N:21]2[CH2:22][CH2:23][N:18]([CH2:17][CH2:16][CH2:15][OH:14])[C:19](=[O:25])[C@@H:20]2[CH3:24])=[O:9])[CH:10]=[CH:11][C:12]=1[F:13]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27736443-(3-Chloro-4-fluorophenyl)prop-2-enoic acidHCID 66999467(S)-1-(3-Hydroxy-propyl)-3-methyl-piperazin-2-one

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 44541810(S)-4-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-1-(3-hydroxy-propyl)-3-methyl-piperazin-2-oneYield 168.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-chloro-4-fluorocinnamic acid (4.52 g, 21.9 mmol), (S)-1-(3-hydroxy-propyl)-3-methyl-piperazin-2-one (3.76 g, 21.9 mmol), N,N-diisopropylethylamine (8.46 g, 65.5 mmol), 1-hydroxybenzotriazole (3.25 g, 24.0 mmol), and N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (4.60 g, 24.0 mmol) in N,N-dimethylformamide (80 ml) was stirred at room temperature for 18 h, then partitioned between 1 M aq. hydrochloric acid solution and ethyl acetate. The organic layer was washed with 1 M aq. hydrochloric acid solution, sat. aq. sodium hydrogencarbonate solution, and brine, dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; CH2Cl2/MeOH/NH4OH 90:10:0.25) produced the title compound (6.54 g, 84%). Colorless gum, MS (ISP)=355.2 (M+H)+.

Workup

  1. custompartitioned between 1 M aq. hydrochloric acid solution and ethyl acetate
  2. washThe organic layer was washed with 1 M aq. hydrochloric acid solution, sat. aq. sodium hydrogencarbonate solution, and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-66de992757c8403397d08c83cde9234f
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Reaction notes

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