1,2-Dichloroethane → Di-tert-butyl [(3R,6S)-6-(2,3-difluorophenyl)-1-(2-hydroxy-2-methylpropyl)-2-oxoazepan-3-yl]imidodicarbonate

HRID 20150

Reaktionsgleichung

Reaktionsgleichung von HRID 20150
[C:1]([O:5][C:6]([N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@@H:9]([C:23]([OH:25])=O)[CH2:10][CH2:11][C@@H:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[F:22])[CH2:13][NH2:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:34][C:35]([CH3:38])([OH:37])[CH3:36].C(N(C(C)C)CC)(C)C.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>CCO.C(Cl)Cl>[F:22][C:16]1[C:17]([F:21])=[CH:18][CH:19]=[CH:20][C:15]=1[C@H:12]1[CH2:13][N:14]([CH2:34][C:35]([OH:37])([CH3:38])[CH3:36])[C:23](=[O:25])[C@H:9]([N:8]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:10][CH2:11]1

Komponenten

9

Edukt 6

HCID 111,2-DichloroethaneHCID 684091-Chloro-2-methylpropan-2-olHCID 81531Diisopropylethylamine2×HCID 181649HOAtHCID 516892Sodium BicarbonateHCID 67526479(5S)-N2,N2-Bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-D-lysine

Produkt 1

HCID 21114341Di-tert-butyl [(3R,6S)-6-(2,3-difluorophenyl)-1-(2-hydroxy-2-methylpropyl)-2-oxoazepan-3-yl]imidodicarbonateAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of (5S)—N2,N2-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-D-lysine (0.569 g, 1.24 mmol), 1-chloro-2-methyl-2-propanol (0.202 g, 1.86 mmol) and diisopropylethylamine (0.529 g, 4.10 mmol) in EtOH (5 mL) was heated at 75° C. overnight. The reaction was concentrated to dryness, diluted with DCM (20 mL) and EDC (0.358 g, 1.87 mmol), HOAT (0.252 g, 1.87 mmol) were added followed by diisopropylethylamine (0.650 mL, 3.73 mmol). After stirring overnight, NaHCO3 was added, the layers separated and the aqueous phase backwashed with DCM. The combined organics were dried over magnesium sulfate, filtered, concentrated and the residue purified by silica gel chromatography (10%→35% EtOAc/hexanes) to give the title compound (0.21 g). MS 513.1 (M+1). 1H NMR (500 MHz, CD3OD) δ 7.1 (m, 3H), 5.24 (d, J=10.7 Hz, 1H), 4.02 (m, 1H), 3.69 (d, J=13.9 Hz, 1H), 3.60 (d, J=15.1 Hz, 1H), 3.39 (m, 1H), 3.24 (d, J=14.2 Hz, 1H), 2.4 (m, 1H), 2.1 (m, 3H), 1.5 (s, 18H), 1.20 (s, 3H), 1.16 (s, 3H).

Aufarbeitung

  1. concentrationThe reaction was concentrated to dryness
  2. additionwere added
  3. customthe layers separated
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue purified by silica gel chromatography (10%→35% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-7d25c302be2b4ec6987907414a8bffe8
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745427B2

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