Water → [1-(S)-(4-Fluorobenzyl)-2-(3-(S)-hydroxypyrrolidin-1-yl)-2-oxoethyl]carbamic acid tert-butyl ester

HRID 751665Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 751665
[C:1]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH:21][C@H:22]1[CH2:26][CH2:25][NH:24][CH2:23]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C>CN(C=O)C>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)[C:18]([N:24]1[CH2:25][CH2:26][C@H:22]([OH:21])[CH2:23]1)=[O:20])([CH3:5])([CH3:6])[CH3:7]

Komponenten

8

Edukt 6

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733874(3S)-pyrrolidin-3-olHCID 7020910N-(tert-Butoxycarbonyl)-4-fluoro-L-phenylalanine

Produkt 1

HCID 59753540[1-(S)-(4-Fluorobenzyl)-2-(3-(S)-hydroxypyrrolidin-1-yl)-2-oxoethyl]carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of (S)-N-Boc-4-fluorophenylalanine (5.08 g, 17.9 mmol) and (S)-3-hydroxypyrrolidine (1.05 mL, 19.7 mmol) in anhydrous DMF (200 mL), was added DIPEA (6.87 mL, 39.5 mmol) and HOBt.H2O (3.02 g, 19.7 mmol). The reaction mixture was stirred for 10 min at room temperature then EDCI (4.13 g, 21.5 mmol) was added and the resulting mixture stirred for 20 h at rt. The volatiles were removed in vacuo then the residue partitioned between water (200 mL) and ethyl acetate (200 mL). The layers were separated and the aqueous layer extracted with ethyl acetate (3×50 mL). The combined organics were washed with aqueous sodium hydroxide solution (2M, 3×50 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The oily residue was purified via flash chromatography (SiO2, methanol/dichloromethane, 1:19, v/v) to give the title compound as a colourless oil which became a white solid on standing. m/z (ES+)=353 [M+H]+; RT=3.17 min.

Aufarbeitung

  1. stirringthe resulting mixture stirred for 20 h at rt
  2. customThe volatiles were removed in vacuo
  3. customthe residue partitioned between water (200 mL) and ethyl acetate (200 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted with ethyl acetate (3×50 mL)
  6. washThe combined organics were washed with aqueous sodium hydroxide solution (2M, 3×50 mL), brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe oily residue was purified via flash chromatography (SiO2, methanol/dichloromethane, 1:19, v/v)

Quellen und Nachweise

ORD-Eintrag
ord-2dd6b0f4da5f4fcd88bfc6c64e923e39
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07405210B2

Notizen zur Reaktion

Wird geladen…