Water → Boc-4(R)-(naphthalen-1-ylmethoxy)proline

HRID 1856625Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1856625
[C:1]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].Br[CH2:20][C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[CH:23][CH:22]=1.O>C1COCC1>[C:1]([N:8]1[CH2:15][C@H:14]([O:16][CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=[CH:23][CH:22]=2)[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Komponenten

6

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 1378441-(Bromomethyl)naphthalene

Produkt 1

HCID 60099086Boc-4(R)-(naphthalen-1-ylmethoxy)prolineAusbeute 56,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Commercially available Boc-4(R)-hydroxyproline (5.00 g, 21.6 mmol) was dissolved in THF (100 mL) and cooled to 0° C. Sodium hydride (60% dispersion in oil, 1.85 g, 45.4 mmol) was added portionwise over 10 minutes and the suspension was stirred at RT for 1 h. Then, 1-(bromomethyl)naphthalene (8.00 g, 36.2 mmol) (prepared as described in E. A. Dixon et al. Can. J. Chem., (1981), 59, 2629-2641) was added and the mixture was heated at reflux for 18 h. The mixture was poured into water (300 mL) and washed with hexane. The aqueous layer was acidified with 10% aqueous HCl and extracted twice with ethyl acetate. The organic layers were combined and washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (49:49:2 hexane: ethyl acetate: acetic acid) to give the title compound as a colorless oil (4.51 g, 56% yield). 1H NMR (DMSO-d6) indicated the presence of two rotamers: δ 8.05 (m, 1H), 7.94 (m, 1H), 7.29 (d, J=14 Hz, 1H), 7.55-7.45 (m, 4H), 4.96 (m, 2H), 4.26 (br. s, 1H), 4.12 (dd, J=J=8 Hz, 1H), 3.54-3.42 (m, 2H), 2.45-2.34 (m, 1H), 2.07-1.98 (m, 1H:) 1.36 (S, (3/9) 9H), 1.34 (s, (6/9) 9H).

Aufarbeitung

  1. addition, (1981), 59, 2629-2641) was added
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 18 h
  4. washwashed with hexane
  5. extractionextracted twice with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (49:49:2 hexane: ethyl acetate: acetic acid)

Quellen und Nachweise

ORD-Eintrag
ord-340b36c496c74fb8b8be464f698172f8
Quelldatensatz
uspto-grants-2000_11
Patentnummer
US06143715

Notizen zur Reaktion

Wird geladen…