Acetic Acid → 4-[3-((R)-2-Hydroxymethyl-pyrrolidin-1-yl)-propyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester

HRID 559324

Reaktionsgleichung

Reaktionsgleichung von HRID 559324
I([O-])(=O)(=O)=O.[Na+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH:22]=C)[C:16](=[O:24])[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[NH:25]1[CH2:31][CH2:30][CH2:29][C@@H:26]1[CH2:27][OH:28].B.N1C=CC=CC=1.C(O)(=O)C.[OH-].[NH4+]>CC(C)=O.O.ClCCCl.C(O)C.[Os](=O)(=O)(=O)=O>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH2:22][N:25]2[CH2:31][CH2:30][CH2:29][C@@H:26]2[CH2:27][OH:28])[C:16](=[O:24])[CH2:15]1)=[O:13])([CH3:8])([CH3:9])[CH3:10]

Komponenten

11

Edukt 6

HCID 176Acetic AcidHCID 14923Ammonium HydroxideHCID 2723995Borane;pyridineHCID 2724541Prolinol, (R)-HCID 23667635Sodium periodateHCID 57445033Tert-butyl 4-but-3-enyl-3-oxopiperazine-1-carboxylate

Produkt 1

HCID 669995404-[3-((R)-2-Hydroxymethyl-pyrrolidin-1-yl)-propyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl esterAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 30318Osmium TetroxideKatalysatorHCID 111,2-DichloroethaneLösungsmittelHCID 702EthanolLösungsmittelHCID 18366337Propan-2-one--water (1/1)Lösungsmittel

Versuchsvorschrift

Sodium metaperiodate (505 mg, 2.36 mmol) and osmium(VIII) oxide (2.5% solution in tert-butylalcohol, 80 μl, 7.9 μmol) were added at 0° C. to a solution of 4-but-3-enyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (200 mg, 0.79 mmol) in acetone/water 1:1 (10 ml). After 30 min, the reaction mixture was allowed to reach room temperature over 45 min, then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), and evaporated. The crude aldehyde intermediate (3-oxo-4-(3-oxo-propyl)-piperazine-1-carboxylic acid tert-butyl ester) and D-prolinol (95 mg, 0.94 mmol) were dissolved in 1,2-dichloroethane (2 ml), then a freshly prepared solution of pyridine borane complex (8 M in pyridine, 0.24 ml, 1.9 mmol) and acetic acid (170 mg, 2.83 mmol) in ethanol (2 ml) was added dropwise at room temperature. The reaction mixture was stirred overnight, then 25%. aq. ammonium hydroxide solution (0.39 ml) was added, and volatile material was removed by rotary evaporation. The residue was purified by chromatography (SiO2; CH2Cl2/MeOH/NH4OH 80:20:0.25) to afford the title compound (160 mg, 60%). Light brown oil, MS (ISP) −342.1 (M+H)+.

Aufarbeitung

  1. waitto reach room temperature over 45 min
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customvolatile material was removed by rotary evaporation
  7. customThe residue was purified by chromatography (SiO2; CH2Cl2/MeOH/NH4OH 80:20:0.25)

Quellen und Nachweise

ORD-Eintrag
ord-4f2e1e1ecd454331b83e5916560f9a76
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08063042B2

Verknüpfte Notizen

Wird geladen…