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

HRID 559358ノート

反応式

HRID 559358 の反応式
[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]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2 回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 回

生成物 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-one収率 41%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-0e005bb4c3804084bf73ccddbe4bda2b
出典データセット
uspto-grants-2011_11
特許番号
US08063042B2

反応ノート

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