Hydrochloric Acid → 4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-1-[3-((R)-2-hydroxymethyl-pyrrolidin-1-yl)-propyl]-piperazin-2-one

HRID 559358Notes

Reaction equation

HRID 559358 reaction equation
[ClH:1].[C:2]([O:6][C:7]([N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][N:18]2[CH2:22][CH2:21][CH2:20][C@@H:19]2[CH2:23][OH:24])[C:11](=[O:25])[CH2:10]1)=[O:8])(C)(C)C.CN1CC[O:30]CC1.[Cl:33][C:34]1[CH:35]=[C:36]([CH:42]=[CH:43][C:44]=1[Cl:45])[CH:37]=[CH:38]C(O)=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>O1CCOCC1>[CH2:44]([Cl:45])[Cl:1].[CH3:2][OH:6].[NH4+:9].[OH-:30].[Cl:33][C:34]1[CH:35]=[C:36](/[CH:37]=[CH:38]/[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][C@@H:19]3[CH2:23][OH:24])[C:11](=[O:25])[CH2:10]2)=[O:8])[CH:42]=[CH:43][C:44]=1[Cl:45]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 145483-(3,4-Dichlorophenyl)prop-2-enoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 669995404-[3-((R)-2-Hydroxymethyl-pyrrolidin-1-yl)-propyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester2×

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 575504044-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-1-[3-((R)-2-hydroxymethyl-pyrrolidin-1-yl)-propyl]-piperazin-2-oneYield 41%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Hydrogen chloride solution (4 M in 1,4-dioxane, 2 ml) was added to a solution of 4-[3-((R)-2-hydroxymethyl-pyrrolidin-1-yl)-propyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (intermediate 7; 157 mg, 0.46 mmol) in 1,4-dioxane (2 ml), then after 90 min volatile material was removed by rotary evaporation. The residue was taken up in dichloromethane (10 ml), treated with 4-methylmorpholine (232 mg, 2.30 mmol), and the mixture obtained concentrated in vacuo. The residue was taken up in N,N-dimethylformamide (2 ml), then 4-methylmorpholine (232 mg, 2.30 mmol), 3,4-dichlorocinnamic acid (108 mg, 0.48 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (262 mg, 0.69 mmol) were added. The solution was stirred at room temperature for 3 h, then mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2; CH2Cl2/MeOH/NH4OH 80:20:0.25) produced the title compound (82 mg, 41%). Colorless gum, MS (ISP)=440.3 (M+H)+.

Workup

  1. customafter 90 min volatile material was removed by rotary evaporation
  2. customthe mixture obtained
  3. concentrationconcentrated in vacuo
  4. custommixture was partitioned between water and ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-0e005bb4c3804084bf73ccddbe4bda2b
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Reaction notes

Loading…