Diisopropyl diazene-1,2-dicarboxylate → 4-Benzyl-6-[(4-fluoro-3-methylphenoxy)methyl]-3-methyl-1,4-oxazepane

HRID 467488Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 467488
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH2:15]([N:22]1[CH2:28][CH:27]([CH2:29][OH:30])[CH2:26][O:25][CH2:24][CH:23]1[CH3:31])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36](O)=[CH:35][C:34]=1[CH3:40]>ClCCl>[CH2:15]([N:22]1[CH2:28][CH:27]([CH2:29][O:30][C:36]2[CH:37]=[CH:38][C:33]([F:32])=[C:34]([CH3:40])[CH:35]=2)[CH2:26][O:25][CH2:24][CH:23]1[CH3:31])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Komponenten

5

Edukt 3

HCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 27373944-Fluoro-3-methylphenolHCID 58405257(4-Benzyl-3-methyl-1,4-oxazepan-6-yl)methanol

Produkt 1

HCID 584052564-Benzyl-6-[(4-fluoro-3-methylphenoxy)methyl]-3-methyl-1,4-oxazepane

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Diisopropyl azodicarboxylate (40 uL, 0.20 mmol, 1.2 equiv) was added to a suspension of (4-benzyl-3-methyl-1,4-oxazepan-6-yl)methanol (4-5, 40 mg, 0.17 mmol, 1 equiv), 4-fluoro-3-methylphenol (26 mg, 0.20 mmol, 1.2 equiv), and polystyrene-supported triphenylphosphine resin (250 mg, 0.51 mmol, 3.0 equiv) in anhydrous dichloromethane (30 mL) at 23° C. The mixture was stirred for 20 h, then filtered. The filtrate was concentrated and the residue was purified by flash column chromatography (20% EtOAc in hexanes) to provide 4-benzyl-6-[(4-fluoro-3-methylphenoxy)methyl]-3-methyl-1,4-oxazepane (4-6) as a ˜1:1 mixture of diastereomers (colorless oil). 1H NMR (300 MHz, CDCl3, reported for a single diasteromer) δ 7.38-7.19 (m, 5H), 6.85 (ddd, 1H,J=12.5, 9.2, 3.7 Hz), 6.53 (m, 2H), 3.97-3.50 (m, 6H), 3.08 (m, 1H), 3.00 (dd, 1H,J=14.0, 4.0 Hz), 2.90 (d, 1H,J=13.7 Hz), 2.82 (dd, 1H,J=14.0, 3.0 Hz), 2.60 (d, 1H,J=13.7 Hz), 2.44 (m, 1H), 2.21 (s w/small splittings, 3H), 1.08 (d, 3H,J=6.7 Hz). LRMS m/z (M+H) 344.4 found, 344.2 required.

Aufarbeitung

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated
  3. customthe residue was purified by flash column chromatography (20% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-a0e7f1dc17b741f59223dd060c3eaaed
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623863B2

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